ATP synthase oligomerization: from the enzyme models to the mitochondrial morphology.
Mitochondrial F(1)F(o) ATP synthase is an enzymatic complex involved in the aerobic synthesis of ATP. It is well known that several enzymes are organized in supramolecular complexes in the inner mitochondrial membrane. The ATP synthase supramolecular assembly is mediated through two interfaces. One leads to dimer formation and the other to oligomer formation. In yeast, the presence of ATP synthase oligomers has been described as essential to the maintenance of the mitochondrial cristae ultrastructure. Indeed, the destabilization of the interactions between monomers was shown to alter the organization of the inner mitochondrial membrane, leading to the formation of onion-like structures similar to those observed in some mitochondrial pathologies. By using information obtained this decade (structure modeling, electron microscopy and cross-linking), this paper (i) reviews the actual state of the art and (ii) proposes a topological model of the transmembrane domains and interfaces of the ATP synthase's tetramer. This review also discusses the physiological role of this oligomerization process and its potential implications in mammal pathology. This article is part of a Directed Issue entitled: Bioenergetic Dysfunction, adaptation and therapy.
University of Bordeaux, IBGC, UMR 5095, F-33000 Bordeaux, France.
Johan
J
Habersetzer
Widade
W
Ziani
Isabelle
I
Larrieu
Claire
C
Stines-Chaumeil
Marie-France
MF
Giraud
Daniel
D
Brèthes
Alain
A
Dautant
Patrick
P
Paumard
D000818:Animals; D019281:Dimerization; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism
D029701:Saccharomyces cerevisiae Proteins; C474451:F1F0-ATP synthase; D025261:Mitochondrial Proton-Translocating ATPases