ATP5MC2: Mitochondrial ATP Synthase Subunit c (Locus 2) in Human OpenAI o3-deep-research-2025-06-26 102 citations 2025-11-03T21:37:59.445810

ATP5MC2: Mitochondrial ATP Synthase Subunit c (Locus 2) in Human

Overview and Gene Context

ATP5MC2 (also known as ATP synthase F0 complex subunit c2, formerly ATP5G2) encodes one of the proteolipid subunits of the mitochondrial F1F0 ATP synthase (also called Complex V of the respiratory chain) (www.ncbi.nlm.nih.gov) (bioinf.umbc.edu). This enzyme complex is responsible for the final step of oxidative phosphorylation, synthesizing ATP from ADP and inorganic phosphate using the proton gradient across the inner mitochondrial membrane (www.proteinatlas.org) (pmc.ncbi.nlm.nih.gov). In human cells, oxidative phosphorylation via ATP synthase provides the majority of cellular ATP (pmc.ncbi.nlm.nih.gov), underscoring the crucial role of this complex in energy metabolism. The ATP synthase is a rotary enzyme consisting of two linked multi-subunit domains: the soluble F1 catalytic sector and the membrane-bound F0 proton-translocating sector (www.proteinatlas.org). Subunit c (the product of ATP5MC2) is a fundamental component of the F0 sector, forming part of the proton-conducting rotor ring embedded in the inner mitochondrial membrane (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Gene family and isoforms: Uniquely, humans have three nuclear genes (ATP5MC1, ATP5MC2, ATP5MC3 – formerly ATP5G1, ATP5G2, ATP5G3) that each encode an identical mature c subunit protein (pmc.ncbi.nlm.nih.gov). These genes arose by duplication and have different precursor leader sequences for mitochondrial import, but their processed products are the same, ensuring robust production of this essential subunit (pmc.ncbi.nlm.nih.gov) (www.ncbi.nlm.nih.gov). There is no strong tissue-specific expression among the three isoforms – all are ubiquitously expressed, reflecting the universal requirement for ATP synthesis (pmc.ncbi.nlm.nih.gov). The human genome also contains multiple pseudogenes of ATP5MC loci (www.ncbi.nlm.nih.gov), highlighting the evolutionary importance and high conservation of this gene family. In keeping with its function, ATP5MC2 mRNA is found in all energy-demanding tissues (e.g. high expression in heart and skeletal muscle) (www.ncbi.nlm.nih.gov). The ATP5MC2 protein is synthesized in the cytosol with an N-terminal mitochondrial targeting peptide and is imported into mitochondria as a precursor (sometimes called ATPase protein 9 or proteolipid 9) (bioinf.umbc.edu). The targeting sequence is cleaved, yielding the mature subunit c (~75 amino acids) that embeds in the inner mitochondrial membrane.

Protein Structure and Localization

Subunit c structure: The subunit c protein is a small hydrophobic protein consisting of two transmembrane α-helices connected by a short loop (pubmed.ncbi.nlm.nih.gov). Each subunit c contains a highly conserved acidic residue in its transmembrane region that serves as the proton-binding site crucial for the enzyme’s proton translocation mechanism (pmc.ncbi.nlm.nih.gov). In many species (e.g. bacteria), this key residue is an aspartate or glutamate (Asp-61 in E. coli c-subunit), which accepts and releases protons during the rotary catalysis cycle. The human subunit c similarly has a conserved carboxylate in its helix that cycles between protonated and deprotonated states as protons pass (pmc.ncbi.nlm.nih.gov). Because of its hydrophobic nature, subunit c is often termed a proteolipid. Multiple c subunits assemble together in the membrane to form a ring-shaped oligomer (the c-ring). High-resolution structural studies show that in mammals this c-ring is composed of 8 identical subunits arranged in a ring within the inner membrane (pmc.ncbi.nlm.nih.gov). This stoichiometry (8 c subunits per ring) is one of the smallest known among F-type ATP synthases, whereas other organisms have larger rings (e.g. yeast has 10, some bacteria up to 15–17) (pmc.ncbi.nlm.nih.gov). The ring of 8 c-subunits is tightly associated with a single copy of subunit a (MT-ATP6 gene product) in the F0 domain, and together they form the proton channel: protons travel through paired half-channels in subunit a and bind to sites on the c-ring, causing it to rotate (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The c-ring is also mechanically linked to the central stalk of the ATP synthase (made of γ, δ, ε subunits) (pmc.ncbi.nlm.nih.gov), which connects into the F1 catalytic head. Through this arrangement, proton-driven rotation of the c-ring is transmitted to the γ-subunit rotor inside F1.

Mitochondrial localization: ATP5MC2’s protein product operates inside mitochondria, specifically in the inner mitochondrial membrane. Within the inner membrane, ATP synthase complexes tend to assemble into dimers and rows along the curved ridges of cristae membranes (pmc.ncbi.nlm.nih.gov). Subunit c is located in the membrane-embedded F0 portion of each monomer, with its proton-binding site accessible at the interface between the c-ring and subunit a on the matrix side vs. intermembrane space side alternately (pmc.ncbi.nlm.nih.gov). The c subunits are integral membrane proteins, oriented such that protons from the intermembrane space bind to the c-ring via subunit a’s input channel, and after a nearly full rotation, are released into the mitochondrial matrix via subunit a’s output channel (pmc.ncbi.nlm.nih.gov). This transmembrane localization is essential: by spanning the inner membrane, the c-ring connects the electrochemical proton gradient (high H+ in the intermembrane space, low in the matrix) to the mechanical rotation used for ATP synthesis. Consistent with this, immunolocalization and proteomic surveys categorize ATP5MC2 as an intracellular membrane protein of the mitochondria (www.proteinatlas.org) (www.proteinatlas.org). It is not found outside the cell; its function is confined to the mitochondria, where it forms part of the inner membrane machinery that produces ATP.

Function in ATP Synthesis

Catalytic role in ATP production: The primary function of the ATP5MC2 gene product (subunit c) is as a core component of the rotary engine that drives ATP synthesis. Mitochondrial F1F0-ATP synthase as a whole catalyzes the reaction:
[ \text{ADP} + \text{Pi} + 4H^+{\text{out}} \rightarrow \text{ATP} + H_2O + 4H^+, ]}
in which ADP and inorganic phosphate are combined to form ATP, powered by the flow of protons down their gradient (from intermembrane space to matrix). The F1 sector (α3β3 catalytic hexamer) contains the nucleotide-binding sites where ADP is phosphorylated to ATP (www.proteinatlas.org). However, without the F0 sector and its rotary mechanism, the F1 would not have the energy input to drive this endergonic reaction. Subunit c, as part of F0, transduces proton-motive force into mechanical rotation: each proton that binds to a c-subunit induces the c-ring to rotate a fraction of a turn, carrying that proton to the opposite side of the membrane (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The central stalk (γδε subunits) rotates in unison with the c-ring and periodically induces conformational changes in the catalytic sites of F1. This is the basis of the rotational catalysis (binding-change) mechanism first proposed by Paul Boyer. As the γ-subunit rotates inside the α3β3> head, it forces each catalytic β-subunit to cycle through different conformations (loose, tight, open) that bind ADP/Pi, synthesize ATP, and release ATP sequentially (pmc.ncbi.nlm.nih.gov). Subunit c’s role is to provide the proton-driven torque for this rotation. Each c-subunit in the ring carries one proton at a time (pmc.ncbi.nlm.nih.gov), so the number of c-subunits in the ring determines how many protons are needed for one full 360° rotation and thus how many protons per ATP are required (pmc.ncbi.nlm.nih.gov). In humans and other mammals with an 8-membered c-ring, one full rotation of the ring (8 protons translocated) drives the synthesis of 3 ATP (since there are three catalytic sites in F1). This implies a proton/ATP ratio of about 2.7 H+ per ATP under physiological conditions (pmc.ncbi.nlm.nih.gov). (By contrast, organisms with larger c-rings require more protons per turn; for example, some bacterial ATP synthases have 10–15 c subunits, meaning ~10 H+/3 ATP (pmc.ncbi.nlm.nih.gov).) The efficient coupling in humans helps maximize ATP yield from the proton gradient.

Notably, the human body’s demand for ATP is enormous – it is estimated that an average person turns over an amount of ATP roughly equal to their body weight each day (pmc.ncbi.nlm.nih.gov). The ATP synthase complex’s high efficiency and continuous operation are what make this massive ATP turnover possible. F1F0-ATP synthase operates near equilibrium, adjusting its activity based on proton-motive force and ATP/ADP levels. Under normal aerobic conditions, it runs in the forward direction to make ATP. However, the enzyme is reversible: if the proton gradient collapses (e.g. during ischemia or in the absence of oxygen), the ATP synthase can hydrolyze ATP to pump protons out of the matrix, acting as an ATPase. In vivo, a small regulatory protein, IF1, inhibits ATP hydrolysis by the F1 sector when mitochondrial membrane potential falls, to prevent wasting ATP (pmc.ncbi.nlm.nih.gov). Thus, ATP5MC2’s product contributes to ATP synthesis under physiologic conditions and can participate in ATP hydrolysis (proton pumping) in pathological conditions, although the latter is normally restrained.

Substrate specificity: Within the ATP synthase complex, the substrates are ADP and inorganic phosphate (for the F1 catalytic sites) and protons (H+) for the F0 channel. The c subunit itself specifically binds protons; it does not interact with ADP/ATP directly. Instead, its “substrate” could be considered the proton – each subunit c binds a proton on a conserved carboxylate and carries it across the membrane until it is released on the opposite side (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The F1 sector’s β-subunits bind ADP/ATP, with a strict specificity for adenine nucleotides (e.g. ATP vs. GTP). The overall enzyme is highly efficient and does not typically produce other products; its reaction specificity is essentially fixed to ATP synthesis/hydrolysis from ADP and Pi. The coupling of proton transport to ATP synthesis is tight: normally, protons cannot leak through the c-ring without driving ATP production, and ATP cannot be hydrolyzed without pumping protons, ensuring efficiency (though see below for pathological uncoupling scenarios).

Biological Pathways and Processes

Oxidative phosphorylation: ATP5MC2 operates in the core of the oxidative phosphorylation (OXPHOS) pathway, a process that couples electron transport to ATP production in mitochondria. It is a part of the multi-step respiratory chain, which includes Complexes I–IV building up an electrochemical proton gradient, and Complex V (ATP synthase) using that gradient to generate ATP. Subunit c (with subunit a) forms the proton channel that allows protons to flow back into the mitochondrial matrix, dissipating the proton motive force created by upstream complexes (pmc.ncbi.nlm.nih.gov). The energy released by this proton flux is converted into mechanical work (rotation of the c-ring) and then into chemical bond energy in ATP (pmc.ncbi.nlm.nih.gov). In essence, subunit c is at the ** nexus between the proton circuit and ATP synthesis**: it is where proton movement is directly tied to the phosphorylation of ADP. This coupling mechanism is the basis of Mitchell’s chemiosmotic theory, confirmed by decades of biochemical and structural studies. Given this role, ATP5MC2 and its sister genes are absolutely essential for cellular energy homeostasis – without functional c subunits, the F1F0 complex cannot rotate and ATP production via OXPHOS ceases. Cells and tissues that rely heavily on aerobic ATP supply (brain, heart, muscle) are especially vulnerable to dysfunction in this component.

Assembly and other interactions: The assembly of the ATP synthase involves combining the F1 sector (α, β, γ, δ, ε subunits encoded by nuclear genes) with the membrane F0 sector (a subunit from mitochondrial DNA, plus b, c, d, e, f, g, F6, etc. from nuclear genes). Subunit c monomers first oligomerize into the c-ring, which then attaches to the F1 sector during enzyme assembly (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Dedicated assembly factors (e.g. ATPAF2 in humans) assist in incorporating subunit c into the rotor structure and ensuring the ring properly associates with subunit a and the peripheral stalk (pmc.ncbi.nlm.nih.gov). Interestingly, studies in yeast and mammals suggest the F1-c-ring assembly can occur separately from other parts, and then later merge with the peripheral stalk and subunit a-containing module (pubmed.ncbi.nlm.nih.gov). This modular assembly underscores how critical proper c-ring formation is – even partial loss of c subunit can stall assembly and lead to “vestigial” complexes lacking the rotor function (pmc.ncbi.nlm.nih.gov). In human cell models completely lacking all three c-subunit genes, assembly is severely impaired: a partial F1 complex may still form and insert in the membrane, but it cannot produce ATP (pmc.ncbi.nlm.nih.gov). Cells compensate by upregulating any remaining isoforms; indeed, the presence of three isoform genes may provide a buffer, as non-mutated isoforms can still supply functional subunits if one gene is defective (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Regulation: At the gene expression level, ATP5MC2 (like the other ATP5MC genes) is generally constitutively expressed in all tissues to meet basal metabolic needs. Nuclear respiratory factors (NRF1/2) and PGC-1α are known to co-regulate many OXPHOS genes, likely including ATP5MC2, to increase ATP synthase content in response to energetic demands. Post-translationally, subunit c function can be modulated by inhibitors or ion conditions rather than classic signaling pathways. For example, oligomycin, a well-known antibiotic inhibitor of ATP synthase, binds to the c-ring (at the interface with subunit a) and blocks the proton channel (pmc.ncbi.nlm.nih.gov). Oligomycin binding essentially “locks” the rotor, preventing proton translocation and thus ATP synthesis – this is why oligomycin is used experimentally to inhibit ATP synthase. Another inhibitor, bedaquiline (a drug used to treat tuberculosis), targets the F0 sector by binding the interface of subunit c and subunit a (ATP6) in mycobacterial ATP synthase (pmc.ncbi.nlm.nih.gov). Bedaquiline is highly specific for bacterial enzymes but at high concentrations can also bind the human enzyme’s c-a interface, slowing proton transport (pmc.ncbi.nlm.nih.gov). These inhibitors underscore the central role of subunit c in the enzyme’s proton channel and have been invaluable tools for probing ATP synthase function.

Beyond small-molecule inhibitors, no dedicated signaling proteins are known to bind subunit c directly in order to regulate ATP synthase activity; rather, the enzyme’s activity is tuned by substrate availability (ADP, proton motive force) and by the IF1 inhibitor protein under certain conditions as noted above (pmc.ncbi.nlm.nih.gov). In terms of metabolic integration, ATP synthase (Complex V) works in concert with upstream complexes I–IV; decreased function in subunit c will cause a buildup of proton motive force (if electron transport continues) until it feedback-inhibits the respiratory chain. Thus, the entire OXPHOS system is delicately balanced, and subunit c is one of the critical throttle points of this system.

Recent Insights and Clinical Significance

Structural and mechanistic insights: Advancements in cryo-electron microscopy in the last decade have greatly deepened understanding of ATP5MC2’s protein product within the holo-enzyme. High-resolution structures of mammalian ATP synthase (e.g. bovine heart mitochondrial enzyme, which is highly similar to human) were resolved in 2015–2020, revealing the exact arrangement of subunits and lipid interactions (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These studies confirmed that the c8 ring is the rotor core and visualized how it contacts subunit a and the peripheral stalk. For instance, a 2020 cryo-EM structure by Walker and colleagues showed the c-ring in three rotational states and supported a proton translocation mechanism via a “Grotthuss chain” of water molecules leading to the proton-binding Asp/Glu on subunit c (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This provides a detailed picture of how protons likely hop along hydrogen-bonded networks to reach the c subunit’s binding site and cause rotation, then exit on the opposite side. The same structural analyses also identified how the peripheral stalk (including subunit b, d, F6, OSCP and others) braces the complex and prevents the catalytic head from co-rotating with the c-ring (pmc.ncbi.nlm.nih.gov). These insights are not only of basic scientific interest but have biomedical relevance: understanding the precise structure of subunit c and its contacts has informed drug development (e.g., rational improvements of bedaquiline analogs to selectively hit bacterial c-rings) and opened avenues to investigate mitochondrial diseases caused by subtle mutations in the ATP synthase. Indeed, researchers have noted that high-resolution maps of the ATP synthase can guide therapies for disorders of oxidative phosphorylation (pmc.ncbi.nlm.nih.gov).

Pathogenic variants: Given the essential role of subunit c, it is perhaps not surprising that germline mutations in ATP5MC2 itself have not been commonly observed – a complete loss-of-function would likely be lethal at the cellular or organismal level. However, recent studies have identified dominant missense mutations in the ATP5MC3 gene (which encodes the same c subunit protein) associated with milder heritable diseases. Notably, in 2021–2022, several patients were reported with early-onset isolated dystonia (a movement disorder) caused by heterozygous mutations in subunit c genes (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). For example, an ATP5MC3 variant p.Asn106Lys (N106K) was found de novo in two unrelated children who developed dystonia in childhood, and another family had an inherited ATP5MC3 Pro107Ala variant with similar symptoms (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These individuals had relatively specific neurological symptoms without the multi-system failure that usually accompanies severe OXPHOS defects. Biochemical analysis in patient cells showed partial ATP synthase dysfunction, suggesting these mutations subtly impair rotor function but not enough to abrogate all ATP production. Intriguingly, these mutations showed incomplete penetrance – some carriers remained asymptomatic (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Researchers speculate that the presence of multiple isoform genes in humans allows compensation: if one allele of ATP5MC3 is mutant, the other isoforms (ATP5MC1, ATP5MC2) may still supply sufficient functional subunits in some individuals (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This underscores an important point: the three ATP5MC genes likely buffer against each other’s defects, which is why isolated mutations produce variable phenotypes. It also highlights that even a single-residue change in the c subunit can reduce ATP synthase efficiency enough to cause disease, especially in tissues like neurons that are highly sensitive to energy supply. Apart from these rare genetic cases, more common human diseases can indirectly involve subunit c. For instance, reductions in ATP5MC2 expression have been observed in certain cancers and neurodegenerative conditions as part of broader mitochondrial dysfunction, though those are typically secondary effects rather than primary mutations (pmc.ncbi.nlm.nih.gov).

Role in mitochondrial permeability transition: One of the most intriguing developments in recent research is the suggested involvement of the ATP synthase c-ring in forming the mitochondrial permeability transition pore (mPTP) – a large non-specific channel whose opening leads to cell death (necrosis or apoptosis) during stress. For decades, the molecular identity of the mPTP was elusive (pmc.ncbi.nlm.nih.gov). In 2013–2017, some studies proposed that the ATP synthase itself (particularly the Fo sector) might double as the pore under certain conditions (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In particular, experiments by Bonora, Bernardini, and colleagues suggested that dimers of ATP synthase could rearrange to form a pore, with subunit c potentially lining the channel. More directly, a 2022 biochemical study (Hsueh et al., Cell Reports 2022) purified the human c-ring and showed that the free c-ring can form a high-conductance, Ca²⁺-activated channel in lipid bilayers, with properties similar to the mPTP (pubmed.ncbi.nlm.nih.gov). Strikingly, they found that adding back the F1 sector (the catalytic head) closed this channel, and conversely, dissociation of F1 from F0 in cells (during ischemic or excitotoxic stress) seemed to trigger pore opening (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). In cellular models, knocking down subunit c prevented calcium-induced mitochondrial swelling and the large conductance pore activity associated with mPTP, supporting the idea that the c-ring is a critical pore-forming component (pubmed.ncbi.nlm.nih.gov). These findings led to a model in which the c-ring constitutes the pore itself when not plugged by the F1 rotor/stator, essentially making the ATP synthase a design where the removal of F1 uncaps a latent channel through the c-ring (pubmed.ncbi.nlm.nih.gov).

However, this hypothesis remains controversial. Recent genetic evidence argues that the ATP synthase is not the primary structure of the mPTP, but rather modulates it. In late 2023, Pekson et al. published a study in PNAS where they genetically removed or depleted ATP synthase components in human cells and in mouse hearts (pmc.ncbi.nlm.nih.gov). If the c-ring were the pore, one would expect eliminating it to abolish mPTP opening. Instead, the researchers found that cells lacking subunit c (or other ATP synthase subunits) could still undergo permeability transition – in fact, the loss of ATP synthase made mitochondria more susceptible to Ca²⁺-induced mPTP opening (pmc.ncbi.nlm.nih.gov). In patch-clamp recordings, mitochondria without a functional ATP synthase still exhibited the characteristic ~1 nS conductance pore openings that were sensitive to cyclosporine A (an mPTP inhibitor), indicating mPTP activity persisted (pmc.ncbi.nlm.nih.gov). The absence of subunit c did not abolish the pore but did seem to remove a brake on its opening, leading to earlier onset of pore opening and greater cell death in stress conditions (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The authors concluded that intact ATP synthase actually serves as a negative regulator of mPTP, possibly by structurally sequestering or stabilizing components that would otherwise form the pore (pmc.ncbi.nlm.nih.gov). In vivo, heart-specific ATP synthase depletion led to larger infarcts upon ischemia-reperfusion, consistent with loss of ATP synthase exacerbating mPTP-driven injury (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Reconciled, the current understanding is that subunit c (the c-ring) has the inherent ability to form a non-specific channel if not constrained – supporting the earlier biochemical studies – but within an intact ATP synthase, the c-ring is normally held in check. Only when the enzyme complex disintegrates (for example, if F1 dissociates during extreme calcium overload or proteolysis) might the c-ring cluster contribute to a pathological pore (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). This area is under active investigation, as it has major implications for developing mPTP inhibitors: some compounds (like oligomycin) that bind subunit c have been reported to inhibit mPTP opening (pmc.ncbi.nlm.nih.gov), while others that bind different parts of ATP synthase can have opposite effects (pmc.ncbi.nlm.nih.gov). Overall, the emerging picture is that ATP5MC2’s gene product is not only central to life-sustaining ATP production but, in dire conditions, can also be involved in cell death mechanisms if the normal assembly of the enzyme is compromised. This duality highlights the evolutionary balance between efficient energy production and the potential risk of dysregulated channel formation.

Conclusions

ATP5MC2 encodes an indispensable component of the mitochondrial ATP synthase, specifically one of the subunit c proteins that form the proton-conducting rotor. The subunit’s primary function is to enable the conversion of a proton gradient into rotary mechanical energy, which is then used to drive ATP synthesis – the fundamental energy-currency-generating process in cells (www.proteinatlas.org). Structurally, ATP5MC2’s product is a small, membrane-embedded proteolipid that assembles into an 8-member ring in the inner mitochondrial membrane (pmc.ncbi.nlm.nih.gov). It works as part of a highly conserved rotary machine present in nearly all forms of life (pmc.ncbi.nlm.nih.gov). The c-ring’s rotation underpins the catalytic mechanism that produces ATP from ADP and phosphate, making subunit c a key player in cellular energy homeostasis. In addition to this well-established role, recent research has unveiled new dimensions to subunit c’s importance – from high-resolution structural details of how it binds protons and interacts with drugs, to its involvement in pathological channels like the mPTP under conditions of stress. Mutations or dysfunction in subunit c can lead to serious consequences, evidenced by rare human diseases (like neurodegenerative syndromes) linked to ATP5MC subunit variants (pmc.ncbi.nlm.nih.gov) and by the fact that many metabolic disorders converge on mitochondrial ATP synthase impairment (pmc.ncbi.nlm.nih.gov).

In summary, ATP5MC2’s gene product ATP synthase subunit c is a cornerstone of the bioenergetic machinery: it localizes to the mitochondrial inner membrane and provides the rotating proton channel that couples the electron transport chain to ATP generation. Its activity exemplifies the ingenious harnessing of electrochemical gradients in biology. As an essential cog in the world’s smallest rotary motor, subunit c enables cells to meet their vast ATP demands – from powering muscle contraction to fueling neuronal firing – thereby supporting virtually every biological process that requires energy (pmc.ncbi.nlm.nih.gov). Continued research into ATP5MC2 and its protein will no doubt further illuminate how energy efficiency, regulation, and cellular survival are interconnected at the molecular level, and may reveal new therapeutic targets within this ancient and vital protein complex.

References: The information above is sourced from recent scientific literature and reviews. Key references include structural studies of ATP synthase (e.g. Walker et al. 2020, PNAS (pmc.ncbi.nlm.nih.gov)), authoritative reviews on ATP synthase mechanism and evolution (Nirody et al. 2020 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov)), as well as up-to-date findings on the role of subunit c in the permeability transition pore (Pekson et al. 2023 (pmc.ncbi.nlm.nih.gov); Hsueh et al. 2022 (pubmed.ncbi.nlm.nih.gov)). Additional details on gene isoforms and clinical mutations were drawn from genetics studies and databases (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These and other cited sources provide experimental evidence and expert analysis underpinning the functions, processes, and significance of ATP5MC2 and its protein product.

Citations

  1. AnnotationURLCitation(end_index=473, start_index=348, title='ATP5MC2 ATP synthase membrane subunit c locus 2 [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene?Cmd=DetailsSearch&Db=gene&Term=517#:~:text=subunits,provided%20by')
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  7. AnnotationURLCitation(end_index=2287, start_index=2176, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=of%20subunit%20c%20%28c_,6')
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  14. AnnotationURLCitation(end_index=4312, start_index=4132, title='ATP5MC2 ATP synthase membrane subunit c locus 2 [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene?Cmd=DetailsSearch&Db=gene&Term=517#:~:text=channel%20and%20they%20specify%20precursors,25%20other%20tissues%20See%20more')
  15. AnnotationURLCitation(end_index=4738, start_index=4521, title='Results for the protein: Q06055', type='url_citation', url='https://bioinf.umbc.edu/dmdm/gene_prot_page.php?id=461592&search_type=protein#:~:text=Image%20AT5G2_HUMAN%20RecName%3A%20Full%3DATP%20synthase,Full%3DATPase%20subunit%20c%3B%20Flags%3A%20Precursor')
  16. AnnotationURLCitation(end_index=5211, start_index=5063, title='Proton-translocating carboxyl of subunit c of F1Fo H(+)-ATP synthase: the unique environment suggested by the pKa determined by 1H NMR - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/8519776/#:~:text=Skip%20to%20main%20page%20content,hairpin%20of%20two%20alpha%20helices')
  17. AnnotationURLCitation(end_index=5516, start_index=5394, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=Each%20c,ratio%20of%20ions%20per%20ATP')
  18. AnnotationURLCitation(end_index=5964, start_index=5842, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=Each%20c,ratio%20of%20ions%20per%20ATP')
  19. AnnotationURLCitation(end_index=6465, start_index=6302, title='Structure of the dimeric ATP synthase from bovine mitochondria - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7519299/#:~:text=bound%20rotor%20consists%20of%20a,into%20the%20extrinsic%20globular%20catalytic')
  20. AnnotationURLCitation(end_index=6795, start_index=6656, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=Rotor%20ring%20stoichiometry%20ranges%20from,Pogoryelov')
  21. AnnotationURLCitation(end_index=7197, start_index=7086, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=of%20subunit%20c%20%28c_,6')
  22. AnnotationURLCitation(end_index=7361, start_index=7198, title='Structure of the dimeric ATP synthase from bovine mitochondria - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7519299/#:~:text=bound%20rotor%20consists%20of%20a,into%20the%20extrinsic%20globular%20catalytic')
  23. AnnotationURLCitation(end_index=7633, start_index=7470, title='Structure of the dimeric ATP synthase from bovine mitochondria - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7519299/#:~:text=bound%20rotor%20consists%20of%20a,into%20the%20extrinsic%20globular%20catalytic')
  24. AnnotationURLCitation(end_index=8266, start_index=8093, title='Structure of the dimeric ATP synthase from bovine mitochondria - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7519299/#:~:text=Mitochondrial%20ATP%20synthases%20occupy%20the,polypeptide%20chains%20of%2017%20different')
  25. AnnotationURLCitation(end_index=8614, start_index=8503, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=of%20subunit%20c%20%28c_,6')
  26. AnnotationURLCitation(end_index=8992, start_index=8881, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=of%20subunit%20c%20%28c_,6')
  27. AnnotationURLCitation(end_index=9517, start_index=9393, title='ATP5MC2 gene information - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000135390-ATP5MC2/summary/gene#:~:text=Protein%20class,i%7D%206')
  28. AnnotationURLCitation(end_index=9714, start_index=9518, title='ATP5MC2 gene information - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000135390-ATP5MC2/summary/gene#:~:text=PROTEIN%20FUNCTION%20Protein%20function%20%28UniProt%29,central%20stalk%20subunits%20to%20proton')
  29. AnnotationURLCitation(end_index=10749, start_index=10581, title='ATP5MC2 gene information - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000135390-ATP5MC2/summary/gene#:~:text=synthase%20or%20Complex%20V,central%20stalk%20subunits%20to%20proton')
  30. AnnotationURLCitation(end_index=11271, start_index=11149, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=Each%20c,ratio%20of%20ions%20per%20ATP')
  31. AnnotationURLCitation(end_index=11410, start_index=11272, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=subunit%20c,with%20%CE%B3%20subunit%2C%20which%20fits')
  32. AnnotationURLCitation(end_index=12067, start_index=11910, title='Structure of the dimeric ATP synthase from bovine mitochondria - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7519299/#:~:text=by%20respiration%2C%20into%20the%20catalytic,These%20structural%20changes')
  33. AnnotationURLCitation(end_index=12330, start_index=12208, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=Each%20c,ratio%20of%20ions%20per%20ATP')
  34. AnnotationURLCitation(end_index=12607, start_index=12485, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=Each%20c,ratio%20of%20ions%20per%20ATP')
  35. AnnotationURLCitation(end_index=13048, start_index=12909, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=Rotor%20ring%20stoichiometry%20ranges%20from,Pogoryelov')
  36. AnnotationURLCitation(end_index=13361, start_index=13222, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=Rotor%20ring%20stoichiometry%20ranges%20from,Pogoryelov')
  37. AnnotationURLCitation(end_index=13768, start_index=13615, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=The%20use%20of%20ATP%20as,continually%20regenerate%20ATP%20from%20the')
  38. AnnotationURLCitation(end_index=14664, start_index=14502, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=ATPases%20are%20regulated%20by%20a,stalk%2C%20except%20through%20a%20confusing')
  39. AnnotationURLCitation(end_index=15495, start_index=15384, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=of%20subunit%20c%20%28c_,6')
  40. AnnotationURLCitation(end_index=15634, start_index=15496, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=subunit%20c,with%20%CE%B3%20subunit%2C%20which%20fits')
  41. AnnotationURLCitation(end_index=16947, start_index=16836, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=of%20subunit%20c%20%28c_,6')
  42. AnnotationURLCitation(end_index=17228, start_index=17090, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=subunit%20c,with%20%CE%B3%20subunit%2C%20which%20fits')
  43. AnnotationURLCitation(end_index=18455, start_index=18313, title='Assembly of human mitochondrial ATP synthase through two separate intermediates, F1-c-ring and b-e-g complex - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/26297831/#:~:text=intermediates%2C%20F1,casings%20fixed%20with%20the%20peripheral')
  44. AnnotationURLCitation(end_index=18624, start_index=18456, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=subunit%20c%20is%20encoded%20by,expression%20and%20ultimately%20produce%20identical')
  45. AnnotationURLCitation(end_index=18947, start_index=18818, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=subunit%20c%20into%20inner%20mitochondrial,8')
  46. AnnotationURLCitation(end_index=19295, start_index=19153, title='Assembly of human mitochondrial ATP synthase through two separate intermediates, F1-c-ring and b-e-g complex - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/26297831/#:~:text=intermediates%2C%20F1,casings%20fixed%20with%20the%20peripheral')
  47. AnnotationURLCitation(end_index=19661, start_index=19484, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=the%20cells%20completely%20lacking%20all,expression%20and%20ultimately%20produce%20identical')
  48. AnnotationURLCitation(end_index=20039, start_index=19862, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=the%20cells%20completely%20lacking%20all,expression%20and%20ultimately%20produce%20identical')
  49. AnnotationURLCitation(end_index=20418, start_index=20250, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=subunit%20c%20is%20encoded%20by,expression%20and%20ultimately%20produce%20identical')
  50. AnnotationURLCitation(end_index=20592, start_index=20419, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=Similarly%2C%20the%20very%20mild%20course,onset%20patients%20have%20severe%20progressive')
  51. AnnotationURLCitation(end_index=21409, start_index=21243, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=Oligomycin%2C%20which%20binds%20subunit%20c,to%20the%20previous%20studies%2C%20we')
  52. AnnotationURLCitation(end_index=21911, start_index=21783, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=%28bz,to%20the%20previous%20studies%2C%20we')
  53. AnnotationURLCitation(end_index=22194, start_index=22066, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=%28bz,to%20the%20previous%20studies%2C%20we')
  54. AnnotationURLCitation(end_index=22842, start_index=22680, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=ATPases%20are%20regulated%20by%20a,stalk%2C%20except%20through%20a%20confusing')
  55. AnnotationURLCitation(end_index=23853, start_index=23696, title='Structure of the dimeric ATP synthase from bovine mitochondria - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7519299/#:~:text=by%20respiration%2C%20into%20the%20catalytic,These%20structural%20changes')
  56. AnnotationURLCitation(end_index=23993, start_index=23854, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=Rotor%20ring%20stoichiometry%20ranges%20from,Pogoryelov')
  57. AnnotationURLCitation(end_index=24545, start_index=24390, title='Structure of the dimeric ATP synthase from bovine mitochondria - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7519299/#:~:text=The%20structure%20of%20the%20dimeric,wedge%20is%20provided%20by%20three')
  58. AnnotationURLCitation(end_index=24703, start_index=24546, title='Structure of the dimeric ATP synthase from bovine mitochondria - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7519299/#:~:text=by%20respiration%2C%20into%20the%20catalytic,These%20structural%20changes')
  59. AnnotationURLCitation(end_index=25265, start_index=25089, title='Structure of the dimeric ATP synthase from bovine mitochondria - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7519299/#:~:text=brings%20about%20structural%20changes%20in,subunit%20a%20constitute%20the%20enzyme%E2%80%99s')
  60. AnnotationURLCitation(end_index=25936, start_index=25786, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=match%20at%20L846%20particular%2C%20to,Further%2C%20investigations')
  61. AnnotationURLCitation(end_index=26710, start_index=26537, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=Similarly%2C%20the%20very%20mild%20course,onset%20patients%20have%20severe%20progressive')
  62. AnnotationURLCitation(end_index=26879, start_index=26711, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=dystonia%20or%20spasmodic%20dysphonia,extremity%20spasticity%2C%20and%20LA%20%5B131')
  63. AnnotationURLCitation(end_index=27271, start_index=27098, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=Similarly%2C%20the%20very%20mild%20course,onset%20patients%20have%20severe%20progressive')
  64. AnnotationURLCitation(end_index=27440, start_index=27272, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=dystonia%20or%20spasmodic%20dysphonia,extremity%20spasticity%2C%20and%20LA%20%5B131')
  65. AnnotationURLCitation(end_index=28005, start_index=27868, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=families%20,were%20identified%20in%20both%20families')
  66. AnnotationURLCitation(end_index=28167, start_index=28006, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=with%20early%20or%20late%20onset%2C,were%20identified%20in%20both%20families')
  67. AnnotationURLCitation(end_index=28576, start_index=28408, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=subunit%20c%20is%20encoded%20by,expression%20and%20ultimately%20produce%20identical')
  68. AnnotationURLCitation(end_index=28750, start_index=28577, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=Similarly%2C%20the%20very%20mild%20course,onset%20patients%20have%20severe%20progressive')
  69. AnnotationURLCitation(end_index=29624, start_index=29467, title='Biological Implications of Differential Expression of Mitochondrial-Shaping Proteins in Parkinson’s Disease - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5789311/#:~:text=Biological%20Implications%20of%20Differential%20Expression,ATP%20synthase')
  70. AnnotationURLCitation(end_index=30207, start_index=30026, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=The%20mitochondrial%20permeability%20transition%20pore,of%20the%20mitochondrial%20ATP%20synthase')
  71. AnnotationURLCitation(end_index=30446, start_index=30357, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=,DOI')
  72. AnnotationURLCitation(end_index=30588, start_index=30447, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=the%20mitochondrial%20permeability%20transition%20in,DOI')
  73. AnnotationURLCitation(end_index=31156, start_index=31015, title='Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35322203/#:~:text=Mitochondrial%20ATP%20synthase%20is%20vital,1%7D%20constitutes')
  74. AnnotationURLCitation(end_index=31555, start_index=31414, title='Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35322203/#:~:text=Mitochondrial%20ATP%20synthase%20is%20vital,1%7D%20constitutes')
  75. AnnotationURLCitation(end_index=31688, start_index=31556, title='Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35322203/#:~:text=the%20inner%20membrane%20during%20cell,subunit%20leak')
  76. AnnotationURLCitation(end_index=32050, start_index=31918, title='Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35322203/#:~:text=the%20inner%20membrane%20during%20cell,subunit%20leak')
  77. AnnotationURLCitation(end_index=32450, start_index=32309, title='Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35322203/#:~:text=Mitochondrial%20ATP%20synthase%20is%20vital,1%7D%20constitutes')
  78. AnnotationURLCitation(end_index=32912, start_index=32786, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=mPTP,it%20instead%20inhibits%20the%20pore')
  79. AnnotationURLCitation(end_index=33369, start_index=33243, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=mPTP,it%20instead%20inhibits%20the%20pore')
  80. AnnotationURLCitation(end_index=33769, start_index=33606, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=Loss%20of%20the%20Mitochondrial%20ATP,Does%20Not%20Affect%20mPTP%20Conductance')
  81. AnnotationURLCitation(end_index=34079, start_index=33953, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=mPTP,it%20instead%20inhibits%20the%20pore')
  82. AnnotationURLCitation(end_index=34253, start_index=34080, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=Depletion%20of%20Assembled%20Mitochondrial%20ATP,Myocardial%20Infarct%20Size%20In%20Vivo')
  83. AnnotationURLCitation(end_index=34580, start_index=34454, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=mPTP,it%20instead%20inhibits%20the%20pore')
  84. AnnotationURLCitation(end_index=34893, start_index=34748, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=The%20mitochondrial%20permeability%20transition%20pore,These')
  85. AnnotationURLCitation(end_index=35067, start_index=34894, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=Depletion%20of%20Assembled%20Mitochondrial%20ATP,Myocardial%20Infarct%20Size%20In%20Vivo')
  86. AnnotationURLCitation(end_index=35673, start_index=35532, title='Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35322203/#:~:text=Mitochondrial%20ATP%20synthase%20is%20vital,1%7D%20constitutes')
  87. AnnotationURLCitation(end_index=35806, start_index=35674, title='Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35322203/#:~:text=the%20inner%20membrane%20during%20cell,subunit%20leak')
  88. AnnotationURLCitation(end_index=36176, start_index=36010, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=Oligomycin%2C%20which%20binds%20subunit%20c,to%20the%20previous%20studies%2C%20we')
  89. AnnotationURLCitation(end_index=36425, start_index=36259, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=Oligomycin%2C%20which%20binds%20subunit%20c,to%20the%20previous%20studies%2C%20we')
  90. AnnotationURLCitation(end_index=37390, start_index=37222, title='ATP5MC2 gene information - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000135390-ATP5MC2/summary/gene#:~:text=synthase%20or%20Complex%20V,central%20stalk%20subunits%20to%20proton')
  91. AnnotationURLCitation(end_index=37702, start_index=37539, title='Structure of the dimeric ATP synthase from bovine mitochondria - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7519299/#:~:text=bound%20rotor%20consists%20of%20a,into%20the%20extrinsic%20globular%20catalytic')
  92. AnnotationURLCitation(end_index=37942, start_index=37794, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=chemical%20reaction%20in%20biological%20systems,Less%20attention')
  93. AnnotationURLCitation(end_index=38746, start_index=38573, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=Similarly%2C%20the%20very%20mild%20course,onset%20patients%20have%20severe%20progressive')
  94. AnnotationURLCitation(end_index=38993, start_index=38843, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=match%20at%20L846%20particular%2C%20to,Further%2C%20investigations')
  95. AnnotationURLCitation(end_index=39762, start_index=39609, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=The%20use%20of%20ATP%20as,continually%20regenerate%20ATP%20from%20the')
  96. AnnotationURLCitation(end_index=40375, start_index=40218, title='Structure of the dimeric ATP synthase from bovine mitochondria - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7519299/#:~:text=by%20respiration%2C%20into%20the%20catalytic,These%20structural%20changes')
  97. AnnotationURLCitation(end_index=40582, start_index=40460, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=Each%20c,ratio%20of%20ions%20per%20ATP')
  98. AnnotationURLCitation(end_index=40722, start_index=40583, title='ATP synthase: Evolution, energetics, and membrane interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7594442/#:~:text=Rotor%20ring%20stoichiometry%20ranges%20from,Pogoryelov')
  99. AnnotationURLCitation(end_index=40963, start_index=40837, title='The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10743364/#:~:text=mPTP,it%20instead%20inhibits%20the%20pore')
  100. AnnotationURLCitation(end_index=41124, start_index=40983, title='Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35322203/#:~:text=Mitochondrial%20ATP%20synthase%20is%20vital,1%7D%20constitutes')
  101. AnnotationURLCitation(end_index=41410, start_index=41233, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=the%20cells%20completely%20lacking%20all,expression%20and%20ultimately%20produce%20identical')
  102. AnnotationURLCitation(end_index=41584, start_index=41411, title='Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11412354/#:~:text=Similarly%2C%20the%20very%20mild%20course,onset%20patients%20have%20severe%20progressive')