title: Age-dependent dissociation of ATP synthase dimers and loss of inner-membrane cristae in mitochondria.
abstract: Aging is one of the most fundamental, yet least understood biological processes that affect all forms of eukaryotic life. Mitochondria are intimately involved in aging, but the underlying molecular mechanisms are largely unknown. Electron cryotomography of whole mitochondria from the aging model organism Podospora anserina revealed profound age-dependent changes in membrane architecture. With increasing age, the typical cristae disappear and the inner membrane vesiculates. The ATP synthase dimers that form rows at the cristae tips dissociate into monomers in inner-membrane vesicles, and the membrane curvature at the ATP synthase inverts. Dissociation of the ATP synthase dimer may involve the peptidyl prolyl isomerase cyclophilin D. Finally, the outer membrane ruptures near large contact-site complexes, releasing apoptogens into the cytoplasm. Inner-membrane vesiculation and dissociation of ATP synthase dimers would impair the ability of mitochondria to supply the cell with sufficient ATP to maintain essential cellular functions.
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Daum
authors.forename: Andreas
authors.initials: A
authors.lastname: Walter
authors.forename: Angelika
authors.initials: A
authors.lastname: Horst
authors.forename: Heinz D
authors.initials: HD
authors.lastname: Osiewacz
authors.forename: Werner
authors.initials: W
authors.lastname: Kühlbrandt
mesh_terms: D000375:Aging / Q000502:physiology*; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism*; D019281:Dimerization; D055032:Electron Microscope Tomography; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000648:ultrastructure; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D048468:Podospora / Q000201:enzymology* / Q000502:physiology
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D025261:Mitochondrial Proton-Translocating ATPases; D021983:Cyclophilins
keywords: cell death; subtomogram averaging