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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Available from: Devrim Acehan, Sep 30, 2015
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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. "
    Biochimica et Biophysica Acta (BBA) - Bioenergetics 04/2015; · 5.35 Impact Factor
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    • "Additionally, CL stabilizes F 1 F O -ATP synthase dimers [10] and respiratory chain supercomplexes [11], affecting mitochondrial morphology [12]. CL normally adopts a bilayer conformation, but when calcium is present in the interface, it assumes a conical inverted shape due to the low hydration of the small polar headgroup [13]. "
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    ABSTRACT: Mitochondria play a key role in adaptation during stressing situations. Cardiolipin, the main anionic phospholipid in mitochondrial membranes, is expected to be determinant in this adaptive mechanism since it modulates the activity of most membrane proteins. Here, we used Saccharomyces cerevisiae subjected to conditions that affect mitochondrial metabolism as a model to determine the possible role of cardiolipin in stress adaptation. Interestingly, we found that thermal stress promotes a 30% increase in the cardiolipin content and modifies the physical state of mitochondrial membranes. These changes have effects on mtDNA stability, adapting cells to thermal stress. Conversely, this effect is cardiolipin-dependent since a cardiolipin synthase-null mutant strain is unable to adapt to thermal stress as observed by a 60% increase of cells lacking mtDNA (ρ(0)). Interestingly, we found that the loss of cardiolipin specifically affects the segregation of mtDNA to daughter cells, leading to a respiratory deficient phenotype after replication. We also provide evidence that mtDNA physically interacts with cardiolipin both in S. cerevisiae and in mammalian mitochondria. Overall, our results demonstrate that the mitochondrial lipid cardiolipin is a key determinant in the maintenance of mtDNA stability and segregation. Copyright © 2015. Published by Elsevier B.V.
    Biochimica et Biophysica Acta 04/2015; 1847(6-7). DOI:10.1016/j.bbabio.2015.03.007 · 4.66 Impact Factor
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