title: Mitochondrial ATP synthase disorders: molecular mechanisms and the quest for curative therapeutic approaches.
abstract: In mammals, the majority of cellular ATP is produced by the mitochondrial F1F(O)-ATP synthase through an elaborate catalytic mechanism. While most subunits of this enzymatic complex are encoded by the nuclear genome, a few essential components are encoded in the mitochondrial genome. The biogenesis of this multi-subunit enzyme is a sophisticated multi-step process that is regulated on levels of transcription, translation and assembly. Defects that result in diminished abundance or functional impairment of the F1F(O)-ATP synthase can cause a variety of severe neuromuscular disorders. Underlying mutations have been identified in both the nuclear and the mitochondrial DNA. The pathogenic mechanisms are only partially understood. Currently, the therapeutic options are extremely limited. Alternative methods of treatment have however been proposed, but still encounter several technical difficulties. The application of novel scientific approaches promises to deepen our understanding of the molecular mechanisms of the ATP synthase, unravel novel therapeutic pathways and improve the unfortunate situation of the patients suffering from such diseases.
authors.affiliation: Institut de Biochimie et Génétique Cellulaires, CNRS-Université Bordeaux2, Bordeaux 33077, France.
authors.forename: Roza
authors.initials: R
authors.lastname: Kucharczyk
authors.forename: Michael
authors.initials: M
authors.lastname: Zick
authors.forename: Maïlis
authors.initials: M
authors.lastname: Bietenhader
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Rak
authors.forename: Elodie
authors.initials: E
authors.lastname: Couplan
authors.forename: Marc
authors.initials: M
authors.lastname: Blondel
authors.forename: Stéphane-Duvezin
authors.initials: SD
authors.lastname: Caubet
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: di Rago
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000201:enzymology* / Q000378:metabolism / Q000628:therapy; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004272:DNA, Mitochondrial; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D025261:Mitochondrial Proton-Translocating ATPases