title: Cardiolipin affects the supramolecular organization of ATP synthase in mitochondria.
abstract: F(1)F(0) ATP synthase forms dimers that tend to assemble into large supramolecular structures. We show that the presence of cardiolipin is critical for the degree of oligomerization and the degree of order in these ATP synthase assemblies. This conclusion was drawn from the statistical analysis of cryoelectron tomograms of cristae vesicles isolated from Drosophila flight-muscle mitochondria, which are very rich in ATP synthase. Our study included a wild-type control, a cardiolipin synthase mutant with nearly complete loss of cardiolipin, and a tafazzin mutant with reduced cardiolipin levels. In the wild-type, the high-curvature edge of crista vesicles was densely populated with ATP synthase molecules that were typically organized in one or two rows of dimers. In both mutants, the density of ATP synthase was reduced at the high-curvature zone despite unchanged expression levels. Compared to the wild-type, dimer rows were less extended in the mutants and there was more scatter in the orientation of dimers. These data suggest that cardiolipin promotes the ribbonlike assembly of ATP synthase dimers and thus affects lateral organization and morphology of the crista membrane.
authors.affiliation: Department of Cell Biology, New York University School of Medicine, New York, New York, USA.
authors.forename: Devrim
authors.initials: D
authors.lastname: Acehan
authors.forename: Ashim
authors.initials: A
authors.lastname: Malhotra
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Mindong
authors.initials: M
authors.lastname: Ren
authors.forename: David L
authors.initials: DL
authors.lastname: Stokes
authors.forename: Michael
authors.initials: M
authors.lastname: Schlame
mesh_terms: D000818:Animals; D002308:Cardiolipins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D005426:Flight, Animal / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics; D008928:Mitochondria / Q000201:enzymology* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000201:enzymology; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism*; D009132:Muscles / Q000201:enzymology / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics
chemical_list: D002308:Cardiolipins; D008565:Membrane Proteins; D017855:Transferases (Other Substituted Phosphate Groups); C100091:cardiolipin synthetase; D025261:Mitochondrial Proton-Translocating ATPases