mitochondrial proton translocating atpases


Summary: Proton-translocating ATPases responsible for ADENOSINE TRIPHOSPHATE synthesis in the MITOCHONDRIA. They derive energy from the respiratory chain-driven reactions that develop high concentrations of protons within the intermembranous space of the mitochondria.

Top Publications

  1. Walker J, Dickson V. The peripheral stalk of the mitochondrial ATP synthase. Biochim Biophys Acta. 2006;1757:286-96 pubmed
    ..However, key issues are unresolved, and so our understanding of the role of the peripheral stalk and the mechanism of synthesis of ATP are incomplete. ..
  2. Bornhovd C, Vogel F, Neupert W, Reichert A. Mitochondrial membrane potential is dependent on the oligomeric state of F1F0-ATP synthase supracomplexes. J Biol Chem. 2006;281:13990-8 pubmed
    ..We propose a role for the supracomplexes of the F1F0-ATP synthase in organizing microdomains within the inner membrane, ensuring optimal bioenergetic competence of mitochondria. ..
  3. Jesina P, Tesarova M, Fornuskova D, Vojtiskova A, Pecina P, Kaplanová V, et al. Diminished synthesis of subunit a (ATP6) and altered function of ATP synthase and cytochrome c oxidase due to the mtDNA 2 bp microdeletion of TA at positions 9205 and 9206. Biochem J. 2004;383:561-71 pubmed
    ..The mutation also affects the biogenesis of COX, which is present in a decreased amount in cells from affected individuals. ..
  4. Villavicencio Queijeiro A, Vázquez Acevedo M, Cano Estrada A, Zarco Zavala M, Tuena de Gómez M, Mignaco J, et al. The fully-active and structurally-stable form of the mitochondrial ATP synthase of Polytomella sp. is dimeric. J Bioenerg Biomembr. 2009;41:1-13 pubmed publisher
    ..Monomer-monomer interactions could be mediated by the membrane-bound subunits ASA6 and ASA9, and may be further stabilized by other polypeptides such as ASA1 and ASA5. ..
  5. Acin Perez R, Fernandez Silva P, Peleato M, Pérez Martos A, Enriquez J. Respiratory active mitochondrial supercomplexes. Mol Cell. 2008;32:529-39 pubmed publisher
    ..Therefore, we have demonstrated the existence of a functional respirasome and propose a structural organization model that accommodates these findings. ..
  6. Ackerman S, Tzagoloff A. Methods to determine the status of mitochondrial ATP synthase assembly. Methods Mol Biol. 2007;372:363-77 pubmed publisher
    ..Studies of such mutants have been instrumental in identifying novel molecular chaperones that act at discrete steps of F1-F0 assembly. Here, we describe some experimental approaches useful in assessing the status of F1-F0 assembly. ..
  7. Rabl R, Soubannier V, Scholz R, Vogel F, Mendl N, Vasiljev Neumeyer A, et al. Formation of cristae and crista junctions in mitochondria depends on antagonism between Fcj1 and Su e/g. J Cell Biol. 2009;185:1047-63 pubmed publisher
    ..We propose a model in which the antagonism between Fcj1 and Su e/g locally modulates the F(1)F(O) oligomeric state, thereby controlling membrane curvature of cristae to generate CJs and cristae tips. ..
  8. Gemin A, Sweet S, Preston T, Singh G. Regulation of the cell cycle in response to inhibition of mitochondrial generated energy. Biochem Biophys Res Commun. 2005;332:1122-32 pubmed
    ..These data provide further evidence that surveillance of available energy occurs during G(1) and ATP deprivation results in cell cycle arrest via a reduction in cyclin D. ..
  9. Wittig I, Schagger H. Supramolecular organization of ATP synthase and respiratory chain in mitochondrial membranes. Biochim Biophys Acta. 2009;1787:672-80 pubmed publisher

More Information


  1. Zick M, Rabl R, Reichert A. Cristae formation-linking ultrastructure and function of mitochondria. Biochim Biophys Acta. 2009;1793:5-19 pubmed publisher
    ..Further, we formulate several theoretical models which could account for the de novo formation of cristae as well as their propagation from existing cristae. ..
  2. Dickson V, Silvester J, Fearnley I, Leslie A, Walker J. On the structure of the stator of the mitochondrial ATP synthase. EMBO J. 2006;25:2911-8 pubmed
    ..It remains unclear whether the transient storage of energy required by the rotary mechanism takes place in the central stalk or in the peripheral stalk or in both domains. ..
  3. Krause F, Reifschneider N, Goto S, Dencher N. Active oligomeric ATP synthases in mammalian mitochondria. Biochem Biophys Res Commun. 2005;329:583-90 pubmed
  4. Brown S, Hosking P, Li J, Williams N. ATP synthase is responsible for maintaining mitochondrial membrane potential in bloodstream form Trypanosoma brucei. Eukaryot Cell. 2006;5:45-53 pubmed
    ..These results support the role of the ATP synthase in the maintenance of the mitochondrial membrane potential in bloodstream form T. brucei. ..
  5. Weimann T, Vaillier J, Salin B, Velours J. The intermembrane space loop of subunit b (4) is a major determinant of the stability of yeast oligomeric ATP synthases. Biochemistry. 2008;47:3556-63 pubmed publisher
  6. Dudkina N, Heinemeyer J, Keegstra W, Boekema E, Braun H. Structure of dimeric ATP synthase from mitochondria: an angular association of monomers induces the strong curvature of the inner membrane. FEBS Lett. 2005;579:5769-72 pubmed
    ..Hence, the function of ATP synthase dimerisation is to control the unique architecture of the mitochondrial inner membrane. ..
  7. Vázquez Acevedo M, Cardol P, Cano Estrada A, Lapaille M, Remacle C, Gonzalez Halphen D. The mitochondrial ATP synthase of chlorophycean algae contains eight subunits of unknown origin involved in the formation of an atypical stator-stalk and in the dimerization of the complex. J Bioenerg Biomembr. 2006;38:271-82 pubmed
    ..The algal enzyme seems to have modified the structural features of its surrounding scaffold, while conserving almost intact the structure of its catalytic subunits. ..
  8. Minauro Sanmiguel F, Wilkens S, Garcia J. Structure of dimeric mitochondrial ATP synthase: novel F0 bridging features and the structural basis of mitochondrial cristae biogenesis. Proc Natl Acad Sci U S A. 2005;102:12356-8 pubmed
    ..On the matrix side of the complex, the two F1 moieties are connected by a protein bridge, which is attributable to the IF1 inhibitor protein. ..
  9. Schnaufer A, Clark Walker G, Steinberg A, Stuart K. The F1-ATP synthase complex in bloodstream stage trypanosomes has an unusual and essential function. EMBO J. 2005;24:4029-40 pubmed
  10. Bisetto E, Di Pancrazio F, Simula M, Mavelli I, Lippe G. Mammalian ATPsynthase monomer versus dimer profiled by blue native PAGE and activity stain. Electrophoresis. 2007;28:3178-85 pubmed
    ..These results suggest that, in native membrane, monomers and dimers are functionally distinct. ..
  11. Buzhynskyy N, Sens P, Prima V, Sturgis J, Scheuring S. Rows of ATP synthase dimers in native mitochondrial inner membranes. Biophys J. 2007;93:2870-6 pubmed
    ..Rotation torque compensation within ATP synthase dimers stabilizes the ATP synthase structure, in particular the stator-rotor interaction. ..
  12. Lefebvre Legendre L, Salin B, Schaeffer J, Brèthes D, Dautant A, Ackerman S, et al. Failure to assemble the alpha 3 beta 3 subcomplex of the ATP synthase leads to accumulation of the alpha and beta subunits within inclusion bodies and the loss of mitochondrial cristae in Saccharomyces cerevisiae. J Biol Chem. 2005;280:18386-92 pubmed
    ..These observations are in accord with other studies in the literature that have pointed to a central role for the ATP synthase in biogenesis of the mitochondrial inner membrane. ..
  13. Arselin G, Vaillier J, Salin B, Schaeffer J, Giraud M, Dautant A, et al. The modulation in subunits e and g amounts of yeast ATP synthase modifies mitochondrial cristae morphology. J Biol Chem. 2004;279:40392-9 pubmed
    ..When doxycycline is removed after five generations, cristae are mainly observed. The data demonstrate that the inner structure of mitochondria depends upon the ability of ATP synthase to make supramolecular structures. ..
  14. Sperl W, Jesina P, Zeman J, Mayr J, DeMeirleir L, VanCoster R, et al. Deficiency of mitochondrial ATP synthase of nuclear genetic origin. Neuromuscul Disord. 2006;16:821-9 pubmed
    ..This phenotype markedly differs from the severe central nervous system changes of ATP synthase disorders caused by mitochondrial DNA mutations of the ATP6 gene presenting mostly as NARP and MILS. ..
  15. Meyer B, Wittig I, Trifilieff E, Karas M, Schagger H. Identification of two proteins associated with mammalian ATP synthase. Mol Cell Proteomics. 2007;6:1690-9 pubmed
    ..The second one had been denoted as diabetes-associated protein in insulin-sensitive tissue (DAPIT), which may provide a clue for further functional and clinical investigations. ..
  16. Houstek J, Pícková A, Vojtiskova A, Mracek T, Pecina P, Jesina P. Mitochondrial diseases and genetic defects of ATP synthase. Biochim Biophys Acta. 2006;1757:1400-5 pubmed
    ..The primary genetic defects have so far been localized in mtDNA ATP6 gene and nuclear ATP12 gene, however, involvement of other nuclear genes is highly probable. ..
  17. Wittig I, Carrozzo R, Santorelli F, Schagger H. Supercomplexes and subcomplexes of mitochondrial oxidative phosphorylation. Biochim Biophys Acta. 2006;1757:1066-72 pubmed
    ..We present a model for a higher supramolecular association of respirasomes into a "respiratory string". ..
  18. Thomas D, Bron P, Weimann T, Dautant A, Giraud M, Paumard P, et al. Supramolecular organization of the yeast F1Fo-ATP synthase. Biol Cell. 2008;100:591-601 pubmed publisher
    ..For a large range of organisms, it has been shown that mitochondrial ATP synthase adopts oligomeric structures. Moreover, several studies have suggested that a link exists between ATP synthase and mitochondrial morphology...
  19. Kenan D, Wahl M. Ectopic localization of mitochondrial ATP synthase: a target for anti-angiogenesis intervention?. J Bioenerg Biomembr. 2005;37:461-5 pubmed
    ..In order to explore the mechanism of action of angiostatin and its mimetics, further work needs to be done to evaluate clinical applicability, specificity, and contraindications for this class of therapeutics. ..
  20. Pogoryelov D, Nikolaev Y, Schlattner U, Pervushin K, Dimroth P, Meier T. Probing the rotor subunit interface of the ATP synthase from Ilyobacter tartaricus. FEBS J. 2008;275:4850-62 pubmed publisher
  21. Zíková A, Schnaufer A, Dalley R, Panigrahi A, Stuart K. The F(0)F(1)-ATP synthase complex contains novel subunits and is essential for procyclic Trypanosoma brucei. PLoS Pathog. 2009;5:e1000436 pubmed publisher
    ..Hence, the two novel proteins appear essential for the structural organization of the functional complex and regulation of mitochondrial energy generation in these organisms is more complicated than previously thought. ..
  22. Reinders J, Wagner K, Zahedi R, Stojanovski D, Eyrich B, van der Laan M, et al. Profiling phosphoproteins of yeast mitochondria reveals a role of phosphorylation in assembly of the ATP synthase. Mol Cell Proteomics. 2007;6:1896-906 pubmed
    ..The authentic phosphoproteome of yeast mitochondria will represent a rich source to uncover novel roles of reversible protein phosphorylation. ..
  23. Wittig I, Schagger H. Structural organization of mitochondrial ATP synthase. Biochim Biophys Acta. 2008;1777:592-8 pubmed publisher
    ..Independent approaches are presented that support previous reports on the existence of ATP synthasomes in the mitochondrial membrane. ..
  24. Wagner K, Rehling P, Sanjuán Szklarz L, Taylor R, Pfanner N, van der Laan M. Mitochondrial F1Fo-ATP synthase: the small subunits e and g associate with monomeric complexes to trigger dimerization. J Mol Biol. 2009;392:855-61 pubmed publisher
    ..We conclude that association of Su e and Su g with monomeric F(1)F(o)-ATP synthase represents an initial step of oligomer formation. ..
  25. Fronzes R, Weimann T, Vaillier J, Velours J, Brèthes D. The peripheral stalk participates in the yeast ATP synthase dimerization independently of e and g subunits. Biochemistry. 2006;45:6715-23 pubmed
  26. Champagne E, Martinez L, Collet X, Barbaras R. Ecto-F1Fo ATP synthase/F1 ATPase: metabolic and immunological functions. Curr Opin Lipidol. 2006;17:279-84 pubmed
    ..Finally, depending on cell type and environment, it can generate ATP or ADP which may transfer a downstream signal to purinergic receptors. ..
  27. Dudkina N, Sunderhaus S, Braun H, Boekema E. Characterization of dimeric ATP synthase and cristae membrane ultrastructure from Saccharomyces and Polytomella mitochondria. FEBS Lett. 2006;580:3427-32 pubmed
    ..These results strongly support the hypothesized role of ATP synthase oligomers in structural determination of the mitochondrial inner membrane. ..
  28. Dudkina N, Heinemeyer J, Sunderhaus S, Boekema E, Braun H. Respiratory chain supercomplexes in the plant mitochondrial membrane. Trends Plant Sci. 2006;11:232-40 pubmed
  29. Chi S, Wahl M, Mowery Y, Shan S, Mukhopadhyay S, Hilderbrand S, et al. Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase. Cancer Res. 2007;67:4716-24 pubmed
    ..Thus, MAb3D5AB1 shows angiostatin-like properties superior to angiostatin and may be exploited in cancer chemotherapy. ..
  30. Strauss M, Hofhaus G, Schröder R, Kuhlbrandt W. Dimer ribbons of ATP synthase shape the inner mitochondrial membrane. EMBO J. 2008;27:1154-60 pubmed publisher
    ..We propose that the mitochondrial ATP synthase organises itself into dimer ribbons to optimise its own performance. ..
  31. Wittig I, Velours J, Stuart R, Schagger H. Characterization of domain interfaces in monomeric and dimeric ATP synthase. Mol Cell Proteomics. 2008;7:995-1004 pubmed publisher
    ..In contrast to the monomer-monomer interface, the interface between dimers in higher oligomeric structures remains largely unknown. However, we could show that the natural inhibitor protein Inh1 is not required for oligomerization. ..
  32. Gavin P, Prescott M, Devenish R. F1F0-ATP synthase complex interactions in vivo can occur in the absence of the dimer specific subunit e. J Bioenerg Biomembr. 2005;37:55-66 pubmed
    ..Moreover, FRET was observed within cells lacking the dimer specific subunit e, indicating structured associations can occur within the inner membrane in the absence of subunit e. ..
  33. Stuart R. Supercomplex organization of the oxidative phosphorylation enzymes in yeast mitochondria. J Bioenerg Biomembr. 2008;40:411-7 pubmed publisher
    ..In addition, the existence of dimeric/oligomeric F(1)F(o)-ATP synthase complexes and their proposed role in establishment of the cristae architecture of the inner mitochondrial membrane shall also be discussed. ..
  34. Dian E, Papatheodorou P, Emmrich K, Randel O, Geissler A, Kölling R, et al. Role of gamma-subunit N- and C-termini in assembly of the mitochondrial ATP synthase in yeast. J Mol Biol. 2008;377:1314-23 pubmed publisher
    ..Yeast strains expressing either of the truncated gamma-subunits did not grow on non-fermentable carbon sources, indicating that non-assembled parts of the ATP synthase accumulated and impaired essential mitochondrial functions. ..
  35. Goyon V, Fronzes R, Salin B, di Rago J, Velours J, Brèthes D. Yeast cells depleted in Atp14p fail to assemble Atp6p within the ATP synthase and exhibit altered mitochondrial cristae morphology. J Biol Chem. 2008;283:9749-58 pubmed publisher
  36. Mayr J, Paul J, Pecina P, Kurnik P, Förster H, Fötschl U, et al. Reduced respiratory control with ADP and changed pattern of respiratory chain enzymes as a result of selective deficiency of the mitochondrial ATP synthase. Pediatr Res. 2004;55:988-94 pubmed
    ..Absence of any mutations in mitochondrial ATP6 and ATP8 genes indicates a nuclear origin of the defect. ..
  37. Giraud M, Paumard P, Soubannier V, Vaillier J, Arselin G, Salin B, et al. Is there a relationship between the supramolecular organization of the mitochondrial ATP synthase and the formation of cristae?. Biochim Biophys Acta. 2002;1555:174-80 pubmed
    ..We provide a model in which the mitochondrial ATP synthase is a key element in cristae morphogenesis. ..
  38. Kominami A. What are the requirements for lysosomal degradation of subunit c of mitochondrial ATPase?. IUBMB Life. 2002;54:89-90 pubmed
  39. Gajewski C, Yang L, Schon E, Manfredi G. New insights into the bioenergetics of mitochondrial disorders using intracellular ATP reporters. Mol Biol Cell. 2003;14:3628-35 pubmed
    ..The severe decrease in nuclear ATP content under "OXPHOS-only" conditions implies that depletion of nuclear ATP plays an important, and hitherto unappreciated, role in patients with mitochondrial dysfunction. ..
  40. Chrzanowska Lightowlers Z, Temperley R, Smith P, Seneca S, Lightowlers R. Functional polypeptides can be synthesized from human mitochondrial transcripts lacking termination codons. Biochem J. 2004;377:725-31 pubmed
  41. Fronzes R, Chaignepain S, Bathany K, Giraud M, Arselin G, Schmitter J, et al. Topological and functional study of subunit h of the F1Fo ATP synthase complex in yeast Saccharomyces cerevisiae. Biochemistry. 2003;42:12038-49 pubmed
    ..Finally, functional characterization of mitochondria from mutants expressing different C-terminal shortened subunit h suggested that its C-terminal part is not essential for the assembly of a functional F1Fo ATP synthase. ..
  42. Hoffmann M, Binder S. Functional importance of nucleotide identities within the pea atp9 mitochondrial promoter sequence. J Mol Biol. 2002;320:943-50 pubmed
    ..The assignment of functionally important nucleotide identities should now facilitate an efficient and reliable prediction of other promoters in mitochondria of dicotyledon plants. ..
  43. Kuhn J, Tengler U, Binder S. Transcript lifetime is balanced between stabilizing stem-loop structures and degradation-promoting polyadenylation in plant mitochondria. Mol Cell Biol. 2001;21:731-42 pubmed
    ..These antagonistic actions thus result in the efficient formation of 3' processed and stable transcripts. ..
  44. Yi L, Jiang F, Chen M, Cain B, Bolhuis A, Dalbey R. YidC is strictly required for membrane insertion of subunits a and c of the F(1)F(0)ATP synthase and SecE of the SecYEG translocase. Biochemistry. 2003;42:10537-44 pubmed
  45. Perrin R, Meyer E, Zaepfel M, Kim Y, Mache R, Grienenberger J, et al. Two exoribonucleases act sequentially to process mature 3'-ends of atp9 mRNAs in Arabidopsis mitochondria. J Biol Chem. 2004;279:25440-6 pubmed
    ..First, AtmtPNPase is involved in removing 3' extensions that may reach several kilobases. Second, AtmtRNaseII degrades short nucleotidic extensions to generate the mature 3'-ends. ..
  46. Bulygin V, Duncan T, Cross R. Rotor/Stator interactions of the epsilon subunit in Escherichia coli ATP synthase and implications for enzyme regulation. J Biol Chem. 2004;279:35616-21 pubmed
    ..Furthermore, the rate of beta-epsilon cross-linking is much faster than that indicated by previous studies, allowing for the possibility of a rapid response to regulatory signals. ..
  47. Gavin P, Prescott M, Luff S, Devenish R. Cross-linking ATP synthase complexes in vivo eliminates mitochondrial cristae. J Cell Sci. 2004;117:2333-43 pubmed
    ..Our findings further suggest that F(1)F(O)-ATPase can exist in oligomeric associations within the membrane during respiratory growth. ..
  48. Velours J, Vaillier J, Paumard P, Soubannier V, Lai Zhang J, Mueller D. Bovine coupling factor 6, with just 14.5% shared identity, replaces subunit h in the yeast ATP synthase. J Biol Chem. 2001;276:8602-7 pubmed
    ..Like subunit h, bovine F(6) is shown to interact mainly with subunit 4 (subunit b), a component of the second stalk of the enzyme. These data indicated the subunit h is the yeast homolog of mammalian coupling factor F(6). ..
  49. Werhahn W, Braun H. Biochemical dissection of the mitochondrial proteome from Arabidopsis thaliana by three-dimensional gel electrophoresis. Electrophoresis. 2002;23:640-6 pubmed
    ..Furthermore, extremely hydrophobic proteins are detectable on the gels. ..
  50. Paumard P, Vaillier J, Coulary B, Schaeffer J, Soubannier V, Mueller D, et al. The ATP synthase is involved in generating mitochondrial cristae morphology. EMBO J. 2002;21:221-30 pubmed
  51. Schagger H. Respiratory chain supercomplexes. IUBMB Life. 2001;52:119-28 pubmed
    ..Dimeric ATP synthase seems to be specific for mitochondrial OXPHOS systems. Monomeric complex V was found in Acetobacterium woodii and Paracoccus denitrificans. ..
  52. Paumard P, Arselin G, Vaillier J, Chaignepain S, Bathany K, Schmitter J, et al. Two ATP synthases can be linked through subunits i in the inner mitochondrial membrane of Saccharomyces cerevisiae. Biochemistry. 2002;41:10390-6 pubmed
  53. Manfredi G, Fu J, Ojaimi J, Sadlock J, Kwong J, Guy J, et al. Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus. Nat Genet. 2002;30:394-9 pubmed
    ..This is the first successful demonstration of allotopic expression of an mtDNA-encoded polypeptide in mammalian cells and could form the basis of a genetic approach to treat a number of human mitochondrial disorders. ..