Cardiolipin Affects the Supramolecular Organization of ATP Synthase in Mitochondria

Department of Cell Biology, New York University School of Medicine, New York, New York, USA.
Biophysical Journal (Impact Factor: 3.97). 05/2011; 100(9):2184-92. DOI: 10.1016/j.bpj.2011.03.031
Source: PubMed


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.

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    • "In particular, CL binding has been considered to be involved in proton uptake at the ubiquinone reduction site [42] and in allowing supercomplex formation with the cytochrome c oxidase [61]. Indeed, thanks to the use of a Δcrd1 mutant of yeast in which the final biosynthesis step of CL is absent [64] [65], CL has been seen to play an active role in supramolecular organization of the mitochondrial respiratory chain through stabilization of supercomplexes [66] [67] [68] [69] [70] [71] or in the oligomerization of the ATP synthase responsible for the cristae morphology [72]. Finally, both the altered level and the fatty acid chain composition of CL have severe impacts on mitochondrial functions and have been linked to a variety of human diseases [73] [74] [75] [76]. "

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    • "Although the lipid profile of the membrane and the lipids bound to the oxidase changed, the requirements for CL were thought to be compensated by the presence of PG, because of its high degree of structural similarity to CL with respect to negative charge and hydrogen bonding capacity (Zhang et al. , 2011a,b ). Moreover , in mitochondria, CL is also required for supramolecular assembly of ATP synthase complexes (Acehan et al. , 2011 ) as well as for respiratory supercomplex formation and stabilization (Pfeiffer et al. , 2003 ). CL stabilizes the respiratory supercomplex formation between cytochrome bc 1 complex and cytochrome c oxidase by neutralizing the charges of lysine residues in the vicinity of their presumed interaction domain. "

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    • "Anionic phospholipids such as phosphatidylglycerol (PG) and cardiolipin (CL) are key components of cellular membranes, where they have important roles in several cellular processes such as energy transduction, stress response, participation in the mechanism of translation coupled to transcription (transertion) in bacteria and the stabilization , maintenance and segregation of mitochondrial DNA [1] [2] [3] [4]. CL was believed to be restricted to the Bacteria and Eukarya domains because early evidence ruled out the existence of this phospholipid in archaeal membranes. "

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