title: Mitochondrial ATP synthase: architecture, function and pathology.
abstract: Human mitochondrial (mt) ATP synthase, or complex V consists of two functional domains: F(1), situated in the mitochondrial matrix, and F(o), located in the inner mitochondrial membrane. Complex V uses the energy created by the proton electrochemical gradient to phosphorylate ADP to ATP. This review covers the architecture, function and assembly of complex V. The role of complex V di-and oligomerization and its relation with mitochondrial morphology is discussed. Finally, pathology related to complex V deficiency and current therapeutic strategies are highlighted. Despite the huge progress in this research field over the past decades, questions remain to be answered regarding the structure of subunits, the function of the rotary nanomotor at a molecular level, and the human complex V assembly process. The elucidation of more nuclear genetic defects will guide physio(patho)logical studies, paving the way for future therapeutic interventions.
authors.affiliation: Department of Pediatrics, Nijmegen Center for Mitochondrial Disorders, 656 Laboratory for Genetic, Endocrine, and Metabolic Disorders, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: An I
authors.initials: AI
authors.lastname: Jonckheere
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Smeitink
authors.forename: Richard J T
authors.initials: RJ
authors.lastname: Rodenburg
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases