query: what is produced in the intermembrane space of mitochondria

pos: Mitochondrial intermembrane space to the cristae (folds of the inner membrane). ADP and a phosphate group are combined to form ATP. Mitochondrial intermembrane space The intermembrane space of a Mitochondrion refers to the compartment formed between the inner and outer mitochondrial membranes. The intermembrane space is chemically similar to cytosol, but includes a large amount of small proteins as well. As electrons move down the proteins in the electron transport chain, the electrons lose energy to bring H+ ions from the mitochondrial matrix into the intermembrane space. As a concentration gradient of hydrogen ions forms, a protein called ATP synthase harnesses the potential

pos: Intermembrane space of the mitochondria, the content of the intermembrane space happens to be similar to that of the content of the cytoplasm. ATP consists of adenosine — composed of an adenine ring and a ribose sugar — and three phosphate groups (triphosphate) The intermembrane space of the chloroplast is exceedingly small, from 10-20 nm thick. Unlike the intermembrane space of the mitochondria, the intermembrane space of the chloroplast does not seem to have any obvious function. Intermembrane space The intermembrane space (IMS) is the region between the inner membrane and the outer membrane of a mitochondrion or a chloroplast. The main

pos: Adenosine triphosphate space. This pumping generates a proton motive force that is the net effect of a pH gradient and an electric potential gradient across the inner mitochondrial membrane. Flow of protons down this potential gradient – that is, from the intermembrane space to the matrix – yields ATP by ATP synthase. Three ATP are produced per turn. Most of the ATP synthesized in the mitochondria will be used for cellular processes in the cytosol; thus it must be exported from its site of synthesis in the mitochondrial matrix. ATP outward movement is favored by the membrane's electrochemical potential because the cytosol

pos: ATP synthase protons movement across the membrane. The F portion of ATP synthase is hydrophilic and responsible for hydrolyzing ATP. This portion is located through the intermembrane space between the inter membrane space of the mitochondria. Subunits formula_2 and formula_3 make a hexamer with 6 binding sites. Three of them are catalytically inactive and they bind ADP. Other three subunits catalyze the ATP synthesis. The other F subunits formula_4 are a part of a rotational motor mechanism. formula_5 subunit allows formula_3 to go through conformational changes, i.e. closed, half open and open states allows for ATP to be bound and released once

pos: Mitochondrial intermembrane space Mitochondrial intermembrane space The intermembrane space of a Mitochondrion refers to the compartment formed between the inner and outer mitochondrial membranes. The intermembrane space is chemically similar to cytosol, but includes a large amount of small proteins as well. As electrons move down the proteins in the electron transport chain, the electrons lose energy to bring H+ ions from the mitochondrial matrix into the intermembrane space. As a concentration gradient of hydrogen ions forms, a protein called ATP synthase harnesses the potential energy of these ions and starts chemiosmosis, where the H+ ions reenter the matrix via this enzyme bound

pos: Eukaryote eukaryote cell by converting sugars into ATP. They have two surrounding membranes, each a phospholipid bi-layer; the inner of which is folded into invaginations called cristae where aerobic respiration takes place. The outer mitochondrial membrane is freely permeable and allows almost anything to enter into the intermembrane space while the inner mitochondrial membrane is semi permeable so allows only some required things into the mitochondrial matrix. Mitochondria contain their own DNA, which has close structural similarities to bacterial DNA, and which encodes rRNA and tRNA genes that produce RNA which is closer in structure to bacterial RNA than to eukaryote

pos: Oxidative phosphorylation ATP. In eukaryotes, these redox reactions are carried out by a series of protein complexes within the inner membrane of the cell's mitochondria, whereas, in prokaryotes, these proteins are located in the cells' intermembrane space. These linked sets of proteins are called electron transport chains. In eukaryotes, five main protein complexes are involved, whereas in prokaryotes many different enzymes are present, using a variety of electron donors and acceptors. The energy released by electrons flowing through this electron transport chain is used to transport protons across the inner mitochondrial membrane, in a process called "electron transport". This generates potential energy

pos: YME1L1 amino acids 317 and 502, an ATP/GTP binding motif, and a HEXXH motif typical of a zinc-dependent binding domain. YME1L1 is embedded in the inner mitochondrial membrane and is more abundant in tissues with a high content of mitochondria such as human adult heart, skeletal muscle, and pancreas RNA. YME1L1 is a member of the AAA family of ATPases and has an important role for the maintenance of mitochondrial morphology. Its mature form assembles into a homo-oligomeric complex within the inner mitochondrial membrane (IM). It degrades both intermembrane space and IM proteins, including lipid transfer proteins, components of protein translocases

pos: Etomoxir Etomoxir Etomoxir, or 2[6(4-chlorophenoxy)hexyl]oxirane-2-carboxylate, is an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) on the outer face of the inner mitochondrial membrane. This prevents the formation of acyl carnitines, a step that is necessary for the transport of fatty acyl chains from the cytosol into the intermembrane space of the mitochondria. This step is essential to the production of ATP from fatty acid oxidation. Etomoxir has also been identified as a direct agonist of PPARα. A double-blind crossover study in human adult males showed that treatment with etomoxir enhanced feelings of hunger and increased meal portion size by 22%. Etomoxir has

pos: Mechanism of action of aspirin are required to attain further inhibition. A side-effect of aspirin mechanism is that the ability of the blood in general to clot is reduced, and excessive bleeding may result from the use of aspirin. Aspirin has been shown to have three additional modes of action. It uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria, by diffusing from the intermembrane space as a proton carrier back into the mitochondrial matrix, where it ionizes once again to release protons. In short, aspirin buffers and transports the protons, acting as a competitor to ATP synthase. When high doses of aspirin are given, aspirin

pos: Etomoxir use of etomoxir as an anti-inflammatory and anticarcinogenic agent. However, the clinical development of etomoxir has been terminated due to severe hepatotoxicity associated with treatment. Etomoxir Etomoxir, or 2[6(4-chlorophenoxy)hexyl]oxirane-2-carboxylate, is an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) on the outer face of the inner mitochondrial membrane. This prevents the formation of acyl carnitines, a step that is necessary for the transport of fatty acyl chains from the cytosol into the intermembrane space of the mitochondria. This step is essential to the production of ATP from fatty acid oxidation. Etomoxir has also been identified as a direct agonist of PPARα. A

pos: Mitochondrial matrix catabolic pathways to proceed favorably for. The electron transport chain and enzymes in the matrix play a large role in the citric acid cycle and oxidative phosphorylation. The citric acid cycle produces NADH and FADH2 through oxidation that will be reduced in oxidative phosphorylation to produce ATP. The cytosolic, intermembrane space, compartment has a water content of 3.8 μl/mg protein, while the mitochondrial matrix 0.8 μl/mg protein. It is not known how mitochondria maintain osmotic balance across the inner mitochondrial membrane, although the membrane contains aquaporins that are believed to be conduits for regulated water transport. Mitochondrial matrix has a

pos: COA6 COA6 Cytochrome c oxidase assembly factor 6 is a protein that in humans is encoded by the "COA6" gene. Mitochondrial respiratory chain Complex IV, or cytochrome c oxidase, is the component of the respiratory chain that catalyzes the transfer of electrons from intermembrane space cytochrome c to molecular oxygen in the matrix and as a consequence contributes to the proton gradient involved in mitochondrial ATP synthesis. The "COA6" gene encodes an assembly factor for mitochondrial complex IV and is a member of the cytochrome c oxidase subunit 6B family. This protein is located in the intermembrane space, associating with SCO2

pos: Uncoupling protein Uncoupling protein An uncoupling protein (UCP) is a mitochondrial inner membrane protein that is a regulated proton channel or transporter. An uncoupling protein is thus capable of dissipating the proton gradient generated by NADH-powered pumping of protons from the mitochondrial matrix to the mitochondrial intermembrane space. The energy lost in dissipating the proton gradient via UCPs is not used to do biochemical work. Instead, heat is generated. This is what links UCP to thermogenesis. UCPs are positioned in the same membrane as the ATP synthase, which is also a proton channel. The two proteins thus work in parallel with one

pos: Mitochondrial matrix The oxidation of NADH and FADH produces GTP from succinyl-CoA synthetase. NADH and FADH2 are produced in the matrix or transported in through porin and transport proteins in order to undergo oxidation through oxidative phosphorylation. NADH and FADH2 undergo oxidation in the electron transport chain by transferring a electrons to regenerate NADand FAD. Protons are pulled into the intermembrane space by the energy of the electrons going through the electron transport chain. Four electrons are finally accepted by oxygen in the matrix to complete the electron transport chain. The protons return to the mitochondrial matrix through the protein ATP synthase.The

pos: Hydrogenosome of a plant or animal is organised very differently from a bacterial cell. Amongst other things, animal and plant cells (which are special cases of what is known as ‘eukaryotic’ cells) contain mitochondria. Mitochondria are like power stations for cells: They supply ATP molecules used throughout the cell as a power source by ‘burning’ carbohydrates and other fuels. They produce carbon dioxide and water as waste. To produce ATP, mitochondria require abundant supplies of oxygen. Some single-celled eukaryotes live in places where oxygen is scarce or non-existent and use hydrogenosomes instead of mitochondria to produce ATP. Mitochondria do not function

pos: Inner mitochondrial membrane cytosol, and the more sequestered space inside the inner membrane, called matrix. For typical liver mitochondria, the area of the inner membrane is about 5 times as large as the outer membrane due to cristae. This ratio is variable and mitochondria from cells that have a greater demand for ATP, such as muscle cells, contain even more cristae. Cristae membranes are studded on the matrix side with small round protein complexes known as F particles, the site of proton-gradient driven ATP synthesis. Cristae affect overall chemiosmotic function of mitochondria. Cristae and the inner boundary membranes are separated by junctions. The

pos: Light-dependent reactions gradient (together with the proton gradient produced by the water-splitting complex in PS II) is used to make ATP via ATP synthase. The similarity in structure and function between cytochrome ' (in chloroplasts) and cytochrome ' ("Complex III" in mitochondria) is striking. Both are transmembrane structures that remove electrons from a mobile, lipid-soluble electron carrier (plastoquinone in chloroplasts; ubiquinone in mitochondria) and transfer them to a mobile, water-soluble electron carrier (plastocyanin in chloroplasts; cytochrome "c" in mitochondria). Both are proton pumps that produce a transmembrane proton gradient. PS I accepts electrons from plastocyanin and transfers them either to NADPH ("noncyclic

pos: Purine nucleotide cycle to dispose AMP produced after following reaction. 2 ADP → ATP + AMP (Catalysed by Adenylyl kinase/Myokinase) Purine nucleotide cycle occurs during strenuous exercise, fasting or starvation when ATP reservoirs run low. 1) Synthesis of fumarate Fumarate is an intermediate of TCA cycle and enters the mitochondria by converting into malate and utilising the malate shuttle where it is converted into Oxaloacetic acid (OAA). OAA either enters into TCA cycle or converts into aspartate in the mitochondria. Aspartate can re-enter purine nucleotide cycle. Oxaloacetic acid + Glutamate ↔ α-Ketoglutarate + Aspartate 2) Synthesis of ammonia (Ammonia genesis) The glutamate produced

pos: UQCRFS1 sequence. The "UQCRFS1" gene encodes for an iron-sulfur protein, which is an essential subunit of the Ubiquinol Cytochrome c Reductase or Complex III in the mitochondrial respiratory chain. Complex III is responsible for electron transfer from coenzyme Q to cytochrome c as well as the proton transfer from the extracellular matrix to the intermembrane space which leads to ATP-coupled electrochemical potential generation. Incorporation of the subunit UQCRFS1 is the second to last step in complex III assembly. Once it is incorporated, UQCRFS1 undergoes proteolytic processing, which is essential for the correct insertion into Complex III. Preventions of the insertion may

pos: Mitochondrial matrix energy is used in order to rotate ATP synthase which facilitates the passage of a proton, producing ATP. A pH difference in the matrix and intermembrane space creates an electrochemical gradient by which ATP synthase can pass a proton into the matrix favorably. The first two steps of the urea cycle take place within the mitochondrial matrix of liver and kidney cells. In the first step ammonia is converted into carbamoyl phosphate through the investment of two ATP molecules. This step is facilitated by carbamoyl phosphate synthetase I. The second step facilitated by ornithine transcarbamylase converts carbamoyl phosphate and ornithine

pos: Thermogenin the mitochondrial matrix. UCP1-mediated heat generation in brown fat uncouples the respiratory chain, allowing for fast substrate oxidation with a low rate of ATP production. UCP1 is related to other mitochondrial metabolite transporters such as the adenine nucleotide translocator, a proton channel in the mitochondrial inner membrane that permits the translocation of protons from the mitochondrial intermembrane space to the mitochondrial matrix. UCP1 is restricted to brown adipose tissue, where it provides a mechanism for the enormous heat-generating capacity of the tissue. UCP1 is activated in the brown fat cell by fatty acids and inhibited by nucleotides. Fatty acids cause

pos: Adenosine triphosphate has a relatively positive charge compared to the relatively negative matrix. For every ATP transported out, it costs 1 H. One ATP costs about 3 H. Therefore, making and exporting one ATP requires 4H The inner membrane contains an antiporter, the ADP/ATP translocase, which is an integral membrane protein used to exchange newly synthesized ATP in the matrix for ADP in the intermembrane space. This translocase is driven by the membrane potential, as it results in the movement of about 4 negative charges out of the mitochondrial membrane in exchange for 3 negative charges moved inside. However, it is also

pos: Electron transport chain pass electrons to a more electronegative acceptor, which in turn donates these electrons to another acceptor, a process that continues down the series until electrons are passed to oxygen, the most electronegative and terminal electron acceptor in the chain. Passage of electrons between donor and acceptor releases energy, which is used to generate a proton gradient across the mitochondrial membrane by actively "pumping" protons into the intermembrane space, producing a thermodynamic state that has the potential to do work. This entire process is called oxidative phosphorylation, since ADP is phosphorylated to ATP using the energy of hydrogen oxidation in many

pos: Reactive oxygen species enough time for the molecule to travel into the nucleus of the cell, subsequently reacting with macromolecules such as DNA. ROS are produced intracellularly through multiple mechanisms and depending on the cell and tissue types, the major sources being the "professional" producers of ROS: NADPH oxidase (NOX) complexes (7 distinct isoforms) in cell membranes, mitochondria, peroxisomes, and endoplasmic reticulum. Mitochondria convert energy for the cell into a usable form, adenosine triphosphate (ATP). The process in which ATP is produced, called oxidative phosphorylation, involves the transport of protons (hydrogen ions) across the inner mitochondrial membrane by means of the electron transport

neg: Mitochondrion degradation of tryptophan. These enzymes include monoamine oxidase, rotenone-insensitive NADH-cytochrome c-reductase, kynurenine hydroxylase and fatty acid Co-A ligase. Disruption of the outer membrane permits proteins in the intermembrane space to leak into the cytosol, leading to certain cell death. The mitochondrial outer membrane can associate with the endoplasmic reticulum (ER) membrane, in a structure called MAM (mitochondria-associated ER-membrane). This is important in the ER-mitochondria calcium signaling and is involved in the transfer of lipids between the ER and mitochondria. The intermembrane space is the space between the outer membrane and the inner membrane. It is also known as perimitochondrial space.

neg: Intermembrane space translocase of the outer mitochondria membrane (TOM) and translocase of the inner mitochondrial membrane (TIM) in mitochondria and translocase of the outer chloroplast membrane (TOC) and translocase of the inner chloroplast membrane (TIC) in chloroplasts. It tends to have a low pH because of the proton gradient which results when protons are pumped from the mitochondrial matrix into the intermembrane space during electron transport. The structures responsible for this are coenzyme Q, NADH coenzyme Q oxidoreductase complex (complex I), succinate-coenzyme Q oxidoreductase complex (complex II), and coenzyme Q-cytochrome c oxidoreductase complex (complex III). Because of channels in the outer membrane

neg: Cytochrome c by removing superoxide (O) and hydrogen peroxide (HO) from mitochondria. Therefore, not only is cytochrome c required in the mitochondria for cell respiration, but it is also needed in the mitochondria to limit the production of O and HO. Cytochrome c is widely believed to be localized solely in the mitochondrial intermembrane space under normal physiological conditions. The release of cytochrome-c from mitochondria to the cytosol, where it activates the caspase family of proteases is believed to be primary trigger leading to the onset of apoptosis. Measuring the amount of cytochrome c leaking from mitochondria to cytosol, and out of

neg: Mitochondria associated membranes chaperones and regulatory proteins which control the formation of the ER–mitochondria junction. Transfer of calcium from ER to mitochondria depends on high concentration of calcium macrodomes in the intermembrane space, and mitochondrial calcium uniporter (MCU) accumulates of calcium into the mitochondrial matrix for electrochemical gradient. Transport of phosphatidylserine into mitochondria from the ER for decarboxylation to phosphatidylethanolamine through the ER-mitochondria lipid which transform phosphatidic acid (PA) into phosphatidylserine (PS) by phosphatidylserine synthases 1 and 2 (PSS1, PSS2) in the ER and then transfers PS to mitochondria, where phosphatidylserine decarboxylase (PSD) transform into phosphatidylethanolamine (PE). PE which is synthesized at mitochondria

neg: Mitochondrion membrane (NADH dehydrogenase (ubiquinone), cytochrome c reductase, and cytochrome c oxidase) perform the transfer and the incremental release of energy is used to pump protons (H) into the intermembrane space. This process is efficient, but a small percentage of electrons may prematurely reduce oxygen, forming reactive oxygen species such as superoxide. This can cause oxidative stress in the mitochondria and may contribute to the decline in mitochondrial function associated with the aging process. As the proton concentration increases in the intermembrane space, a strong electrochemical gradient is established across the inner membrane. The protons can return to the matrix through

neg: Apoptosome involves binding of extracellular ligands to transmembrane receptors, while the intrinsic pathway take place in the mitochondria. This intrinsic pathway involves the release of cytochrome C from the mitochondria and subsequent binding to the cytosolic protein Apaf-1. Cytochrome c release is thus necessary for the initiation of apoptosome action; this release is regulated in a number of ways, most importantly by detection of calcium ion levels. Cytochrome c release is proposed to take place in one of two ways. Firstly, the permeability transition pore (PTP) when the mitochondria receives a death inducing signal, and releases intermembrane space proteins (12). The

neg: Cytochrome c family photosynthetic reaction center of Rhodopseudomonas viridis that contains a tetraheme cytochrome "c" subunit. The attachment of the heme group is physically separated from the protein biosynthesis. Proteins are synthesized within the cytoplasm and endoplasmic reticulum, while the maturation of cytochromes "c" occurs in the periplasm of prokaryots, the intermembrane space of mitochondria or the stroma of chloroplasts. Several biochemical pathways have been discovered that differ depending on organism. Also called cytochrome "c" maturation (ccm) and found in proteobacteria, plant mitochondria, some protozoal mitochondria, deinococci and archaea. Ccm comprises at least eight membrane proteins (CcmABCDEFGH) that are needed for electron transfer

neg: SOD1 another enzyme called catalase. SOD1 has been postulated to localize to the outer mitochondrial membrane (OMM), where superoxide anions would be generated, or the intermembrane space. The exact mechanisms for its localization remains unknown, but its aggregation to the OMM has been attributed to its association with BCL-2. Wildtype SOD1 has demonstrated antiapoptotic properties in neural cultures, while mutant SOD1 has been observed to promote apoptosis in spinal cord mitochondria, but not in liver mitochondria, though it is equally expressed in both. Two models suggest SOD1 inhibits apoptosis by interacting with BCL-2 proteins or the mitochondria itself. Most notably, SOD1

neg: Mitochondrial ROS Mitochondrial ROS Mitochondrial ROS (mtROS or mROS) are reactive oxygen species (ROS) that are produced by mitochondria. Generation of mitochondrial ROS mainly takes place at the electron transport chain located on the inner mitochondrial membrane during the process of oxidative phosphorylation (OXPHOS). Leakage of electrons at complex I and complex III from electron transport chains leads to partial reduction of oxygen to form superoxide. Subsequently, superoxide is quickly dismutated to hydrogen peroxide by two dismutases including superoxide dismutase 2 (SOD2) in mitochondrial matrix and superoxide dismutase 1 (SOD1) in mitochondrial intermembrane space. Collectively, both superoxide and hydrogen peroxide generated in

neg: PrimPol of cases. PrimPol is formed of two protein domains, a catalytic primase-polymerase domain and a zinc finger domain. The primase and polymerase catalytic functions of PrimPol localise to the primase-polymerase domain but primase activity of PrimPol requires the zinc finger domain. PrimPol has been found to be mainly located in the cytosol (47%), with large fractions also found in the mitochondria (34%), and nuclear compartments (19%). The mitochondrial fraction of PrimPol is found to be in the matrix of the mitochondria, as opposed to the either the membrane or intermembrane space. A mutation in the "PRIMPOL" gene has been correlated

neg: Mitochondrion For instance, red blood cells have no mitochondria, whereas liver cells can have more than 2000. The organelle is composed of compartments that carry out specialized functions. These compartments or regions include the outer membrane, the intermembrane space, the inner membrane, and the cristae and matrix. Although most of a cell's DNA is contained in the cell nucleus, the mitochondrion has its own independent genome that shows substantial similarity to bacterial genomes. Mitochondrial proteins (proteins transcribed from mitochondrial DNA) vary depending on the tissue and the species. In humans, 615 distinct types of protein have been identified from cardiac mitochondria,

neg: CEP89 protein contains two coiled-coil domains and a putative mitochondrial-targeting signal. Experiments have shown that CEP89 is found within the intermembrane space, as well as the cytosol of the mitochondria. The "CEP89" gene encodes for a protein required for ciliogenesis. It plays a role in mitochondrial metabolism by modulating complex IV activity. CEP89 has also been shown to be responsible for the integrity of the mitochondria, membrane depolarization, synaptic transmission of photoreceptor neurons and for the synaptic organization of the larval neuromuscular junction. Variants of "CEP89" have been associated with the mitochonrdial Complex IV deficiency, a deficiency in an enzyme complex

neg: Carnitine A attacks the acyl-adenylate, displacing AMP to form thioester fatty acyl-CoA. In the second reaction, the activated fatty acids that are intended for mitochondrial oxidation are transported into the matrix by a carrier protein, but first the acyl-CoA must be transiently attached to the hydroxyl group of carnitine to form fatty acyl–carnitine. This transesterification is catalyzed by an enzyme found in the outer membrane of the mitochondria known as carnitine acyltransferase 1 (also called carnitine palmitoyltransferase 1, CPT1). The fatty acyl–carnitine ester formed then diffuses across the intermembrane space of the mitochondria and enters the matrix by passive transport through

neg: Mitochondrial biogenesis translated in the cell’s cytosol. The resulting unfolded precursor proteins will then be able to reach their respective mitochondrial compartments. Precursor proteins will be transported to one of four areas of the mitochondria, which include the outer membrane, inner membrane, intermembrane space, and matrix. All proteins will enter the mitochondria by a translocase on the outer mitochondrial membrane (TOM). Some proteins will have an N-terminal targeting signal, and these proteins will be detected and transported into the matrix, where they will then be cleaved and folded. Other proteins may have targeting information in their sequences and will not include an

neg: Intermembrane space Intermembrane space The intermembrane space (IMS) is the region between the inner membrane and the outer membrane of a mitochondrion or a chloroplast. The main function of mitochondrial intermembrane space is oxidative phosphorylation. Channel proteins called porins in the outer membrane allow free movement of ions and small molecules into the intermembrane space. This does not mean that it is essentially continuous with the cytosol in terms of the solutes relevant for the functioning of these organelles. Enzymes destined for the mitochondrial matrix or the stroma can pass through the intermembrane space via transport through [1]s. These are known as

neg: Oxidative phosphorylation passing electrons from donors to acceptors, and transporting protons across a membrane. These processes use both soluble and protein-bound transfer molecules. In mitochondria, electrons are transferred within the intermembrane space by the water-soluble electron transfer protein cytochrome c. This carries only electrons, and these are transferred by the reduction and oxidation of an iron atom that the protein holds within a heme group in its structure. Cytochrome c is also found in some bacteria, where it is located within the periplasmic space. Within the inner mitochondrial membrane, the lipid-soluble electron carrier coenzyme Q10 (Q) carries both electrons and protons by

neg: PET100 PET100 PET100 homolog is a protein that in humans is encoded by the "PET100" gene. Mitochondrial complex IV, or cytochrome c oxidase, is a large transmembrane protein complex that is part of the respiratory electron transport chain of mitochondria. The small protein encoded by the "PET100" gene plays a role in the biogenesis of mitochondrial complex IV. This protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. Mutations in this gene are associated with mitochondrial complex IV deficiency. This gene has a pseudogene on chromosome 3. Alternative splicing results in multiple transcript variants. The "PET100"

neg: Neurodegeneration can also form lipoprotein nanoparticles similar to apolipoproteins. The most common form of cell death in neurodegeneration is through the intrinsic mitochondrial apoptotic pathway. This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from the mitochondrial intermembrane space (IMS). Reactive oxygen species (ROS) are normal byproducts of mitochondrial respiratory chain activity. ROS concentration is mediated by mitochondrial antioxidants such as manganese superoxide dismutase (SOD2) and glutathione peroxidase. Over production of ROS (oxidative stress) is a central feature of all neurodegenerative disorders. In addition to the generation of ROS, mitochondria are also involved with life-sustaining functions

neg: Thermogenin Thermogenin Thermogenin (called uncoupling protein by its discoverers and now known as uncoupling protein 1, or UCP1) is an uncoupling protein found in the mitochondria of brown adipose tissue (BAT). It is used to generate heat by non-shivering thermogenesis, and makes a quantitatively important contribution to countering heat loss in babies which would otherwise occur due to their high surface area-volume ratio. UCPs are transmembrane proteins that decrease the proton gradient generated in oxidative phosphorylation. They do this by increasing the permeability of the inner mitochondrial membrane, allowing protons that have been pumped into the intermembrane space to return to

neg: Mitoferrin-1 and increased lifespans of roughly 50-80%. Mitoferrin-1 Mitoferrin-1 (Mfrn1) is a 38 kDa protein that is encoded by the "SLC25A37" gene in humans. It is a member of the Mitochondrial carrier (MC) Superfamily, however, its metal cargo makes it distinct from other members of this family. Mfrn1 plays a key role in mitochondrial iron homeostasis as an iron transporter, importing ferrous iron from the intermembrane space of the mitochondria to the mitochondrial matrix for the biosynthesis of heme groups and Fe-S clusters. This process is tightly regulated, given the redox potential of Mitoferrin’s iron cargo. Mfrn1 is paralogous to Mitoferrin-2

neg: Mitoferrin-1 Mitoferrin-1 Mitoferrin-1 (Mfrn1) is a 38 kDa protein that is encoded by the "SLC25A37" gene in humans. It is a member of the Mitochondrial carrier (MC) Superfamily, however, its metal cargo makes it distinct from other members of this family. Mfrn1 plays a key role in mitochondrial iron homeostasis as an iron transporter, importing ferrous iron from the intermembrane space of the mitochondria to the mitochondrial matrix for the biosynthesis of heme groups and Fe-S clusters. This process is tightly regulated, given the redox potential of Mitoferrin’s iron cargo. Mfrn1 is paralogous to Mitoferrin-2 (Mfrn2), a 39 kDa protein encoded

neg: Arginine:glycine amidinotransferase is located in the cytoplasm, including the intermembrane space of the mitochondria, of the cells that make up those tissues. -Arginine:glycine amidinotransferase catalyses the first, which is also the committed step in the formation of creatine. The second step of the process, producing the actual creatine molecule, occurs solely in the cytosol, where the second enzyme, S-adenosylmethionine:guanidinoacetate methyltransferase (GAMT), is found. The creatine is then transported through the bloodstream and taken up through sodium-dependent creatine transporters by cells that require creatine. The crystal structure of AGAT was determined by Humm, Fritsche, Steinbacher, and Huber of the Max Planck Institute of

neg: Electrochemical gradient animal cell has a transmembrane electrical potential of -50 mV to -70 mV inside the cell relative to the outside. Electrochemical gradients also play a role in establishing proton gradients in oxidative phosphorylation in mitochondria. The final step of cellular respiration is the electron transport chain. Four complexes embedded in the inner membrane of the mitochondrion make up the electron transport chain. However, only complexes I, III, and IV pump protons from the matrix to the intermembrane space (IMS). In total, there are ten protons translocated from the matrix to the IMS which generates an electrochemical potential of more than

neg: CCS (gene) SOD1. CCS's catalytic oxidation of SOD1's disulfide bridge can only be performed in the presence of oxygen. Furthermore, the disulfide linkage of SOD1 can be performed without the presence of CCS but requires oxygen and is much slower. Additionally, CCS is proposed to help the proper folding of SOD1 by binding in the apo-state. As well as SOD1, "CCS" (gene) has been shown to interact with APBA1. CCS is localized in the nucleus, cytosol, and mitochondrial intermembrane space. CCS is imported to the mitochondria by Mia40 and Erv1 disulfide relay system. The cysteine 64 of CCS Domain I generates a

neg: Cytochrome c family proteins CcsB and CcsA. The CcsBA protein complex was suggested to act as a heme transporter during the attachment process. In some organisms such as "Helicobacter hepaticus" both proteins are found as a fused single protein. Apoprotein transport occurs via the Sec translocon as well. Fungal, vertebrate and invertebrate mitochondria produce cytochrome "c" proteins with a single enzyme called HCCS (holocytochrome c synthase) or cytochrome "c" heme lyase (CCHL). The protein is attached to the inner membrane of the intermembrane space. In some organisms, such as "Saccharomyces cerevisiae", cytochrome "c" and cytochrome "c" are synthesized by separate heme lyases, CCHL

neg: Apoptosis-inducing factor prepare for cell death. Recently, researchers have discovered that AIF's activity is dependent upon the type of cell, the apoptotic insult, and its DNA-binding ability. AIF also plays a significant role in the mitochondrial respiratory chain and metabolic redox reactions. The AIF protein is located across 16 exons on the X chromosome in humans. AIF1 (the most abundant type of AIF) is translated in the cytosol and recruited to the mitochondrial membrane and intermembrane space by its N-terminal mitochondrial localization signal (MLS). Inside the mitochondria, AIF folds into its functional configuration with the help of the cofactor flavin adenine dinucleotide

neg: Tim9-Tim10 complex intermembrane space. The intermembrane space import and assembly machinery (MIA) is believed to mediate transport of the small Tim precursors into the intermembrane space subcompartment. MIA is composed of two main essential cysteine-rich proteins; Mia40 and Erv1. Mia40 is also referred to as Tim40 in yeast and deficiency of Mia40 has been reported to affect import of the small Tims. Mia40 is anchored to the mitochondrial inner membrane via an N-terminal hydrophobic segment, exposing a large domain to the intermembrane space. It contains 6 conserved cysteine residues, which allow the binding of incoming Tim precursor proteins. Following import of small

neg: Sorting and assembly machinery into the intermembrane space of mitochondria via the translocase of the outer membrane. Following import, beta barrel proteins are transported to the SAM complex by chaperone complexes, formed by assembly of the small Tim proteins. The complex formed by the three sorting and assembly machinery subunits (SAM core complex), is responsible for the integration of beta barrel proteins into the outer mitochondrial membrane. Mdm10 is another mitochondrial membrane protein that is responsible for maintaining mitochondrial morphology and distribution. It has been found to interact with the SAM core complex and may play a role in assembling Tom40 into the translocase

neg: Translocase of the outer membrane Translocase of the outer membrane The translocase of the outer membrane (TOM) is a complex of proteins found in the outer mitochondrial membrane of the mitochondria. It allows movement of proteins through this barrier and into the intermembrane space of the mitochondrion. Most of the proteins needed for mitochondrial function are encoded by the nucleus of the cell. The outer membrane of the mitochondrion is impermeable to large molecules greater than 5000 Daltons. The TOM works in conjunction with the translocase of the inner membrane (TIM) to translocate proteins into the mitochondrion. Many of the proteins in the TOM complex,

neg: Cytochrome c peroxidase fast growing yeast strains are exhausted, the cells turn to respiration which raises the concentration of mitochondrial HO In addition to its peroxidase activity, it acts as a sensor and a signaling molecule to exogenous HO, which activates mitochondrial catalase activity. In eukaryotes, CCP contain a mono-"b"-type haem cofactor and is targeted to the intermembrane space of the mitochondria. In prokaryotes, CCP contains a "c-"type dihaem cofactor and is localized to the periplasm of the cell. Both enzymes work to resist peroxide-induced cellular stress. CCP plays an integral role in enabling inter-protein biological electron transfer. The negative charge transfer process

neg: Translocase of the outer membrane TOMM22, TOMM40, TOM7, TOMM7 Translocase of the outer membrane The translocase of the outer membrane (TOM) is a complex of proteins found in the outer mitochondrial membrane of the mitochondria. It allows movement of proteins through this barrier and into the intermembrane space of the mitochondrion. Most of the proteins needed for mitochondrial function are encoded by the nucleus of the cell. The outer membrane of the mitochondrion is impermeable to large molecules greater than 5000 Daltons. The TOM works in conjunction with the translocase of the inner membrane (TIM) to translocate proteins into the mitochondrion. Many of the proteins

neg: Carnitine palmitoyltransferase I Carnitine palmitoyltransferase I Carnitine palmitoyltransferase I (CPT1) also known as carnitine acyltransferase I, CPTI, CAT1, CoA:carnitine acyl transferase (CCAT), or palmitoylCoA transferase I, is a mitochondrial enzyme responsible for the formation of acyl carnitines by catalyzing the transfer of the acyl group of a long-chain fatty acyl-CoA from coenzyme A to l-carnitine. The product is often Palmitoylcarnitine (thus the name), but other fatty acids may also be substrates. It is part of a family of enzymes called carnitine acyltransferases. This "preparation" allows for subsequent movement of the acyl carnitine from the cytosol into the intermembrane space of mitochondria. Three isoforms

neg: SOD1 complex and not fully understood, involving the selective binding of copper and zinc ions, formation of the intra-subunit disulfide bond between Cys-57 and Cys-146, and dimerization of the two subunits. The copper chaperone for Sod1 (CCS) facilitates copper insertion and disulfide oxidation. Though SOD1 is synthesized in the cytosol and can mature there, the fraction of expressed, and still immature, SOD1 targeted to the mitochondria must be inserted into the intermembrane space. There, it forms the disulfide bond, though not metalation, required for its maturation. The mature protein is highly stable, but unstable when in its metal-free and disulfide-reduced forms.

neg: Protein disulfide-isomerase intermembrane space of the mitochondria; an example of this is mitochondrial IMS import and assembly (Mia40), which has 2 catalytic domains that contain a CXC, which is similar to the CGHC domain of PDI. PDI displays oxidoreductase and isomerase properties, both of which depend on the type of substrate that binds to protein disulfide-isomerase and changes in protein disulfide-isomerase's redox state. These types of activities allow for oxidative folding of proteins. Oxidative folding involves the oxidation of reduced cysteine residues of nascent proteins; upon oxidation of these cysteine residues, disulfide bridges are formed, which stabilizes proteins and allows for native

neg: HINT2 and localizes to the mitochondria within their cells. Specifically, the protein is located in the inner mitochondrial membrane, facing the mitochondrial matrix. This positioning likely facilitates the transport of cholesterol from the cytosol to the matrix, which is necessary for steroidogenesis, by providing a contact site for the hydrophobic molecule and allowing it to cross the mitochondrial intermembrane space. HINT2 regulates steroidogenesis through calcium-dependent and calcium-independent signalling pathways that may serve to maintain a favorable mitochondrial potential. Its role in calcium homeostasis may also contribute to its proapoptotic function in hepatocytes and other non-steroidogenic cells, though the exact mechanism remains

neg: Apoptosis The two best-understood activation mechanisms are the intrinsic pathway (also called the mitochondrial pathway) and the extrinsic pathway. The "intrinsic pathway" is activated by intracellular signals generated when cells are stressed and depends on the release of proteins from the intermembrane space of mitochondria. The "extrinsic pathway" is activated by extracellular ligands binding to cell-surface death receptors, which leads to the formation of the death-inducing signaling complex (DISC). A cell initiates intracellular apoptotic signaling in response to a stress, which may bring about cell suicide. The binding of nuclear receptors by glucocorticoids, heat, radiation, nutrient deprivation, viral infection, hypoxia, increased

neg: CHCHD10 CHCHD10 Coiled-coil-helix-coiled-coil-helix domain-containing protein 10, mitochondrial, also known as Protein N27C7-4 is a protein that in humans is encoded by the "CHCHD10" gene. The "CHCHD10" gene is located on the q arm of chromosome 22 at position 11.23 and it spans 2,138 base pairs. The "CHCHD10" gene produces a 14.9 kDa protein composed of 149 amino acids. It is enriched at cristae junctions in the intermembrane space of the mitochondria. The structure of the protein contains a nonstructured N-terminal region, a hydrophobic helix and a C-terminal CHCH domain which contains a Cx(9)C motif and two additional cysteines. A total of

neg: AIFM1 apoptotic cells that is found in the mitochondrial intermembrane space in healthy cells. Induction of apoptosis results in the cleavage of this protein at residue 102 by calpains and/or cathepsins into a soluble and proapoptogenic form that translocates to the nucleus, where it effects chromosome condensation and fragmentation. In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. AIFM1 also contributes reductase activity in redox metabolism. Mutations in the AIFM1 gene are correlated with Charcot-Marie-Tooth disease (Cowchock syndrome). At a cellular level, AIFM1 mutations result in deficiencies in oxidative phosphorylation, leading to severe mitochondrial

neg: Translocase of the outer membrane contain amino-terminal presequences that carry information required for the targeting of proteins to the mitochondrial matrix These matrix targeting signals generally contain 10-80 amino acid residues that take on the conformation of an amphipathic-α helix and contain one positive and hydrophobic face. Once the precursor reaches the matrix, the presequence is typically cleaved off by the matrix processing peptidase. Proteins targeted to other sub-compartments of the mitochondria such as the intermembrane space and inner mitochondrial membrane, contain internal targeting signals, these signals have an indefinable nature and are inconsistent in their pattern. Proteins targeted to the outer membrane also contain

neg: Mitochondrial carrier event may have occurred less than 2 billion years ago when mitochondria first developed their specialized endosymbiotic functions within eukaryotic cells. Members of the MC family are functional and structural monomers although early reports indicated that they are dimers. Most MC proteins contain a primary structure exhibiting three repeats, each of about 100 amino acyl residues in length, and both the N and C termini face the intermembrane space. All carriers contain a common sequence, referred to as the MCF motif, in each repeated region, with some variation in one or two signature sequences. Amongst the members of the mitochondrial

neg: Apoptosis-inducing factor seizures, blindness, deafness, etc. These AIF-deficient mouse models are important for fixing complex I deficiencies. The identification of AIF-interacting proteins in the inner mitochondrial membrane and intermembrane space will help researchers identify the mechanism of the signaling pathway that monitors the function of AIF in the mitochondria. Human genes encoding apoptosis inducing factor isozymes include: The apoptotic function of AIFs has been shown in organisms belonging to different eukaryotic organisms including mentioned above human factors: AIM1, AIM2, and AIM3 (Xie "et al.", 2005), yeast factors NDI1 and AIF1 as well as AIF of Tetrahymena. Phylogenetic analysis indicates that the divergence

neg: Membrane contact site mechanism that limits the accumulation of cardiolipin in mitochondria: high cardiolipin concentrations have the final results to inhibit its synthesis and the mitochondrial import of PA. Another study by Lahiri et al. has demonstrated that loss of contacts between the ER and mitochondria results in severe reduction in mitochondrial biosynthesis of phosphatidylethanolamine (PE) due to reduction in transport of phosphatidylserine (PS), which is the precursor for PE synthesis. Membrane contact site Membrane contact sites (MCS) are close appositions between two organelles. Ultrastructural studies typically reveal an intermembrane distance in the order of the size of a single protein, as small

neg: Tim9-Tim10 complex in oxidised state and form disulfide bridges which prevents their escape out of the intermembrane space. Small Tim proteins are then maintained in active conformation within the intermembrane space by Hot13 (helper of Tims). It is possible that Hot13 may have reducing effects on small Tim proteins as they counterbalance the harmful effects that oxidative agents exhibit. Tim9-Tim10 complex Tim9 and Tim10 make up the group of essential small Tim proteins that assist in transport of hydrophobic precursors across the intermembrane space. Both Tim9 and Tim10 form a hexamer, the Tim9-Tim10 complex, that when associated, functions as a chaperone to

neg: Mitochondrion Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules, such as ions and sugars, in the intermembrane space is the same as in the cytosol. However, large proteins must have a specific signaling sequence to be transported across the outer membrane, so the protein composition of this space is different from the protein composition of the cytosol. One protein that is localized to the intermembrane space in this way is cytochrome c. The inner mitochondrial membrane contains proteins with five types of functions: It contains more than 151 different polypeptides, and has a very

neg: Inner mitochondrial membrane Inner mitochondrial membrane The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space. The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. The numerous invaginations of the membrane are called cristae, separated by crista junctions from the inner boundary membrane juxtaposed to the outer membrane. Cristae significantly increases the total membrane surface area compared to a smooth inner membrane and thereby the available working space. The inner membrane creates two compartments. The region between the inner and outer membrane, called the intermembrane space which is largely continuous with the

neg: AK2 AK2 Adenylate kinase 2 is an enzyme that is encoded in humans by the "AK2" gene. The AK2 protein is found in the intermembrane space of the mitochondrion. Adenylate kinases are involved in regulating the adenine nucleotide composition within a cell by catalyzing the reversible transfer of phosphate groups among adenine nucleotides. Three isozymes of adenylate kinase, namely 1, 2, and 3, have been identified in vertebrates; this gene encodes isozyme 2. Expression of these isozymes is tissue-specific and developmentally regulated. Isozyme 2 is localized in the mitochondrial intermembrane space and may play a role in apoptosis. Two transcript variants

neg: Dinoseb Water can cleave off the additional proton to form a neutral compound. The product of this reaction can undergo a second nitration to form dinoseb. Dinoseb is an uncoupler of oxidative phosphorylation. It is a weak acid that can pass through lipid membranes when it’s in the undissociated form. It uses this property to transport protons through the inner mitochondrial membrane(IMM). Protons are taken up from the intermembrane space and after transport through the IMM, they are released again in the mitochondrial matrix. Dinoseb in the dissociated form is negatively charged, which causes it to move to the intermembrane space

neg: Translocase of the inner membrane associate directly with Tim22, is also believed to assist in the stability of Tim22. Unlike cleavable preproteins, following translocation across the outer membrane via the translocase of the outer membrane, carrier preproteins are bound by the soluble Tim9-Tim10 complex of which the majority of this complex (~95%) is free floating within the intermembrane space. It is possible that this small Tim complex is able to stabilise precursor carrier proteins by acting as a chaperone and preventing the hydrophobic precursors from aggregating in the aqueous environment of the intermembrane space. A small portion of Tim9 and Tim10 (~5%) assembles into a

neg: LACTB conserved penicillin-binding protein domain and may therefore be responsible for organelle targeting. LACTB is widely expressed in different mammalian tissues, with the predominant expression in human skeletal muscle. It localizes in the mitochondrial intermembrane space. LACTB can polymerize into stable filaments occupying the mitochondrial intermembrane space. These filaments are speculated to play a role in submitochondrial organization and therefore possibly affect mitochondrial metabolon organization. It has been found LACTB could cause obesity through gene co-expression analysis based on data integrated from multiple sources. This has been validated in vivo through LACTB overexpression in transgenic mice, which resulted in an obese

neg: Cardiolipin to maintain its full enzymatic function. Cytochrome bc1(Complex III) also needs cardiolipin to maintain its quaternary structure and functional role. Complex V of the oxidative phosphorylation machinery also displays high binding affinity for CL, binding four molecules of CL per molecule of complex V. Cardiolipin distribution to the outer mitochondrial membrane would lead to apoptosis of the cells, as evidenced by cytochrome c (cyt c) release, Caspase-8 activation, MOMP induction and NLRP3 inflammasome activation. During apoptosis, cyt c is released from the intermembrane spaces of mitochondria into the cytosol. Cyt c can then bind to the IP3 receptor on endoplasmic

neg: Adenosine triphosphate inner mitochondrial membrane is impermeable to NADH and NAD. Instead of transferring the generated NADH, a malate dehydrogenase enzyme converts oxaloacetate to malate, which is translocated to the mitochondrial matrix. Another malate dehydrogenase-catalyzed reaction occurs in the opposite direction, producing oxaloacetate and NADH from the newly transported malate and the mitochondrion's interior store of NAD. A transaminase converts the oxaloacetate to aspartate for transport back across the membrane and into the intermembrane space. In oxidative phosphorylation, the passage of electrons from NADH and FADH through the electron transport chain pumps protons out of the mitochondrial matrix and into the intermembrane

neg: Coenzyme Q – cytochrome c reductase radical theory of aging). Electron leakage occurs mainly at the Q site and is stimulated by antimycin A. Antimycin A locks the "b" hemes in the reduced state by preventing their re-oxidation at the Q site, which, in turn, causes the steady-state concentrations of the Q semiquinone to rise, the latter species reacting with oxygen to form superoxide. The effect of high membrane potential is thought to have a similar effect. Superoxide produced at the Qo site can be released both into the mitochondrial matrix and into the intermembrane space, where it can then reach the cytosol. This could be

neg: OMA1 acids with mitochondrial transition peptide (position 1-13). The mature protein has a theoretical pI of 8.44. The inner membrane of mitochondrial houses two AAA proteases and these membrane-embedded peptidases were termed m- and i-AAA proteases to indicate their different topology in the inner membrane. The m-AAA protease is facing the matrix and the i-AAA protease is facing the intermembrane space. OMA1 was shown to share an overlapping proteolytic activity with m-AAA protease. However, OMA1 doesn't completely regulate the turnover of a model substrate, Oxa1, as what the m-AAA protease does. On the contrary, Oma1 only generates N- and C-terminal proteolytic

neg: Succinate dehydrogenase b complex with six transmembrane helices containing one heme b group and a ubiquinone-binding site. Two phospholipid molecules, one cardiolipin and one phosphatidylethanolamine, are also found in the SdhC and SdhD subunits (not shown in the image). They serve to occupy the hydrophobic space below the heme b. These subunits are displayed in the attached image. SdhA is green, SdhB is teal, SdhC is fuchsia, and SdhD is yellow. Around SdhC and SdhD is a phospholipid membrane with the intermembrane space at the top of the image. Ubiquinone's binding site, image 4, is located in a gap composed of SdhB,

neg: Chemiosmosis is simply the negative of PMF(import). The spontaneity of proton import (from the P to the N side) is universal in all bioenergetic membranes. This fact was not recognized before the 1990s, because the chloroplast thylakoid lumen was interpreted as an interior phase, but in fact it is topologically equivalent to the exterior of the chloroplast. Azzone et al. stressed that the inside phase (N side of the membrane) is the bacterial cytoplasm, mitochondrial matrix, or chloroplast stroma; the outside (P) side is the bacterial periplasmic space, mitochondrial intermembrane space, or chloroplast lumen. Furthermore, 3D tomography of the mitochondrial inner

neg: Photosynthesis algae, photosynthesis takes place in organelles called chloroplasts. A typical plant cell contains about 10 to 100 chloroplasts. The chloroplast is enclosed by a membrane. This membrane is composed of a phospholipid inner membrane, a phospholipid outer membrane, and an intermembrane space. Enclosed by the membrane is an aqueous fluid called the stroma. Embedded within the stroma are stacks of thylakoids (grana), which are the site of photosynthesis. The thylakoids appear as flattened disks. The thylakoid itself is enclosed by the thylakoid membrane, and within the enclosed volume is a lumen or thylakoid space. Embedded in the thylakoid membrane are

neg: Crista proposed were: NADH is oxidized into NAD, H ions, and electrons by an enzyme. FADH is also oxidized into H ions, electrons, and FAD. As those electrons travel farther through the electron transport chain in the inner membrane, energy is gradually released and used to pump the hydrogen ions from the splitting of NADH and FADH into the space between the inner membrane and the outer membrane (called the intermembrane space), creating an electrochemical gradient. This electrochemical gradient creates potential energy (see "") across the inner mitochondrial membrane known as the proton-motive force. As a result, chemiosmosis occurs, and the

neg: Chloroplast the thylakoids and intermembrane space. The protein-rich, alkaline, aqueous fluid within the inner chloroplast membrane and outside of the thylakoid space is called the stroma, which corresponds to the cytosol of the original cyanobacterium. Nucleoids of chloroplast DNA, chloroplast ribosomes, the thylakoid system with plastoglobuli, starch granules, and many proteins can be found floating around in it. The Calvin cycle, which fixes CO into sugar takes place in the stroma. Chloroplasts have their own ribosomes, which they use to synthesize a small fraction of their proteins. Chloroplast ribosomes are about two-thirds the size of cytoplasmic ribosomes (around 17 nm vs

neg: Humanin Humanin Humanin is a peptide encoded in the mitochondrial genome by the 16S ribosomal RNA gene, MT-RNR2. Its structure contains a three-turn α-helix, and no symmetry. In "in vitro" and animal models, it appears to have cytoprotective effects. Humanin is encoded in the mitochondrial genome by the 16S ribosomal RNA gene, MT-RNR2. The expressed peptide contains a three-turn α-helix, and has no symmetry. The length of the peptide depends on where it is produced. If it is produced inside the mitochondria it will be 21 amino acids long. If it is produced outside the mitochondria, in the cytosol, it will

neg: Arthur L. Horwich As an independent researcher, Horwich asked whether the pathway that imports an enzyme called ornithine transcarbamylase (OTC) into the mitochondria of mammalian cells also could work in yeast. In 1987, during a genetic screen in yeast, Horwich and his colleagues stumbled across a protein folding function inside mitochondria. In the mutant strain, proteins entered mitochondria from the cytosol normally but then misfolded and aggregated. They named the protein encoded by the affected gene HSP60, Heat shock protein 60, because it has a mass of 60 kDa and is produced in larger quantity in response to heat. Hsp60 is found in

neg: Mitochondrion are inherited only through the mother. By contrast, natural selection weeds out mitochondria that reduce female survival as such mitochondria are less likely to be passed on to the next generation. Therefore, it is suggested that human females and female animals tend to live longer than males. The authors claim that this is a partial explanation. Uniparental inheritance leads to little opportunity for genetic recombination between different lineages of mitochondria, although a single mitochondrion can contain 2–10 copies of its DNA. For this reason, mitochondrial DNA is usually thought to reproduce by binary fission. What recombination does take place maintains

neg: PINK1 PINK1/parkin pathway. In addition to mitochondrial fission, PINK1 has been implicated in mitochondrial motility. The accumulation of PINK1 and recruitment of parkin targets a mitochondria for degradation, and PINK1 may serve to enhance degradation rates by arresting mitochondrial motility. Over-expression of PINK1 produced similar effects to silencing Miro, a protein closely associated with mitochondrial migration. Another mechanism of mitochondrial quality control may arise through mitochondria-derived vesicles. Oxidative stress in mitochondria can produce potentially harmful compounds including improperly folded proteins or reactive oxygen species. PINK1 has been shown to facilitate the creation of mitochondria-derived vesicles which can separate reactive oxygen species

neg: Tim9-Tim10 complex Tim proteins into the intermembrane space Mia40 interacts with small Tim proteins via disulfide bonds. Following isomerisation of the disulfide bridge, the polypeptide is released. Mia40 which is now in reduced state, is then oxidised by Erv1. This oxidation step is vital to facilitate further rounds of precursor protein import. Without Erv1 activity, reduced Mia40 accumulates and is in inactive conformation. Interaction between the incoming precursor proteins, Mia40 and Erv1, is maintained as a result of a flow of electrons that are transferred from the incoming protein to Mia40 and from reduced Mia40 to oxidised Erv1. Precursors are then released

neg: PET100 gene is located on the p arm of chromosome 19 in position 13.2 and spans 1,839 base pairs. The gene produces a 9.1 kDa protein composed of 73 amino acids. The encoded protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. This protein's N-terminus is essential for mitochondrial localization. It assembles into a 300 kDA complex which is dependent on the mitochondrial membrane potential, accumulating over time. The protein encoded by "PET100" is involved in Complex IV biogenesis as a COX chaperone; it is required for interaction between MR-1S, PET117, and Complex IV. In 8

neg: Q cycle heme group. The electron is from there transferred to an oxidized molecule of Cytochrome c externally bound to complex III, which then dissociates from the complex. In addition, the reoxidation of the 'FeS protein' releases the proton bound to His181 into the intermembrane space. The other electron, which was transferred to the "b" heme, is used to reduce the "b" heme, which in turn transfers the electron to the ubiquinone bound at the Q site. The movement of this electron is energetically unfavourable, as the electron is moving towards the negatively charged side of the membrane. This is offset by

neg: Mitochondrial fusion occurs. The role of the OPA1 protein is to protect cells against apoptosis by inhibiting the release of cytochrome c. Once this protein is altered, there is a change in the cristae structure, release of cytochrome c, and the activation of the destructive caspase enzymes. These resulting changes indicate that inner mitochondrial membrane structure is linked with regulatory pathways in influencing cell life and death. OPA1 plays both a genetic and molecular role in mitochondrial fusion and in cristae remodeling during apoptosis. OPA1 exists in two forms; the first being soluble and found in the intermembrane space, and the second

neg: COA6 and COX2. It stabilizes newly formed COX2 and is part of the mitochondrial copper relay system. Mutations in this gene result in fatal infantile cardioencephalomyopathy. The "COA6" gene is located on the q arm of chromosome 1 in position 42.2 and spans 10,612 base pairs. The gene produces a 14.1 kDa protein composed of 125 amino acids. The COA6 protein is found a complex with TMEM177, COX20, MT-CO2/COX2, COX18, SCO1 and SCO2. This protein localizes to the intermembrane space, associating with the inner membrane and transmembrane proteins such as SCO2 and COX2. The "COA6" encodes a protein which is an

neg: Coenzyme Q – cytochrome c reductase (2Fe•2S). Structures of complex III: , In vertebrates the bc complex, or Complex III, contains 11 subunits: 3 respiratory subunits, 2 core proteins and 6 low-molecular weight proteins. Proteobacterial complexes may contain as few as three subunits. It catalyzes the reduction of cytochrome "c" by oxidation of coenzyme Q (CoQ) and the concomitant pumping of 4 protons from the mitochondrial matrix to the intermembrane space: In the process called Q cycle, two protons are consumed from the matrix (M), four protons are released into the inter membrane space (IM) and two electrons are passed to cytochrome "c". The reaction mechanism

neg: Oxidative phosphorylation more elaborate than those of the other respiratory complexes, and occurs in two steps called the Q cycle. In the first step, the enzyme binds three substrates, first, QH, which is then oxidized, with one electron being passed to the second substrate, cytochrome c. The two protons released from QH pass into the intermembrane space. The third substrate is Q, which accepts the second electron from the QH and is reduced to Q, which is the ubisemiquinone free radical. The first two substrates are released, but this ubisemiquinone intermediate remains bound. In the second step, a second molecule of QH

neg: Inner mitochondrial membrane by separating the matrix from the cytosolic environment. This compartmentalization is a necessary feature for metabolism. The inner mitochondrial membrane is both an electrical insulator and chemical barrier. Sophisticated ion transporters exist to allow specific molecules to cross this barrier. There are several antiport systems embedded in the inner membrane, allowing exchange of anions between the cytosol and the mitochondrial matrix. Inner mitochondrial membrane The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space. The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. The numerous invaginations of the membrane

neg: Parasite Eve that a scientific study asking citizens what color mitochondria are stated that they are colored green, similar to what was presented in the movie. In 1997, a film adaptation of the "Parasite Eve" novel was released in Japan. "Parasite Eve" was directed by Masayuki Ochiai and written by Ryoichi Kimizuka. The film was produced by Fuji TV and distributed to the United States by ADV Films and by Fuji in Europe. ADV premiered the film on June 18, 2000 for a limited theatrical run. It was later released on DVD on August 14, 2001. The film does not contain an

neg: CKMT1A mitochondrial intermembrane space to Cr to yield ADP plus PCr. As an enzyme central to cell energetics, CKMT1A is often impaired in pathological situations. CKMT1A is known as a primary target of oxidative and radical-induced molecular damage; and the impairment of CKMT1A has been reported in ischaemia, cardiomyopathy, and neurodegenerative disorders due to the failure in maintaining metabolic homeostasis. Overexpression of uMtCK has been reported for several tumors with poor prognosis and this may be the adaption of cancer cells to maintain the high growth rate. CKMT1A Creatine kinase U-type, mitochondrial, also called ubiquitous mitochondrial creatine kinase (uMtCK), is in

neg: SOD1 This manifests in vitro, as the loss of metal ions results in increased SOD1 aggregation, and in disease models, where low metalation is observed for insoluble SOD1. Moreover, the surface-exposed reduced cysteines could participate in disulfide crosslinking and, thus, aggregation. SOD1 binds copper and zinc ions and is one of three superoxide dismutases responsible for destroying free superoxide radicals in the body. The encoded isozyme is a soluble cytoplasmic and mitochondrial intermembrane space protein, acting as a homodimer to convert naturally occurring, but harmful, superoxide radicals to molecular oxygen and hydrogen peroxide. Hydrogen peroxide can then be broken down by

neg: HIGD1A face outward into the intermembrane space while the rest of the protein loops inside the matrix. Though the N-terminal domain is not necessary to direct the localization of HIGD1A, it is required for the survival of the protein. The gene "HIGD1A" is an isoform of "HIMP1-b" via alternative splicing. HIGD1A primarily functions in mitochondrial homeostasis and, thus, cell survival when under conditions of stress, such as hypoxia and glucose deprivation. For instance, HIGD1A promotes survival of pancreatic α and β cells under stress. HIGD1A has also been found in other parts of the brain, heart, liver, and kidney, where it

neg: Cereulide Cereulide Cereulide is a toxin produced by "Bacillus cereus". A cyclic dodecadepsipeptide resembling valinomycin, it contains three repeats of four amino acids: D-Oxy-Leu—D-Ala—L-Oxy-Val—L-Val. It is a potent cytotoxin that destroys mitochondria. Cereulide acts as ionophore with a high affinity to potassium cations. Exposure to cereulide causes loss of the membrane potential and uncoupling of oxidative phosphorylation in the mitochondria. The spores of cereulide-producing strains of "B. cereus" are manyfold more heat resistant than spores of cereulide non-producers. It has no loss of activity upon autoclaving, cooking, or baking. Cereulide is produced by a dedicated non-ribosomal peptide synthesis (NRPS) system in