Cardiolipin Affects the Supramolecular Organization of ATP Synthase in Mitochondria
Cardiolipin Affects the Supramolecular Organization of ATP Synthase in Mitochondria
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DOI：
10.1016/j.bpj.2011.03.031
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发表时间：
2011-05-04
影响因子：
3.4
通讯作者：
Schlame, Michael
中科院分区：
文献类型：
--
作者：
Acehan, Devrim;Malhotra, Ashim;Schlame, Michael
F1F0 ATP合酶形成倾向于组装成大的超分子结构的二聚体。我们发现，心磷脂的存在是至关重要的寡聚化的程度和程度的顺序在这些ATP合酶组件。这一结论是根据对从果蝇飞行肌线粒体中分离的嵴囊泡的冷冻电子断层扫描图的统计分析得出的，这些嵴囊泡非常富含ATP合酶。我们的研究包括一个野生型对照，一个心磷脂合成酶突变体几乎完全丧失心磷脂，和一个tafazzin突变体降低心磷脂水平。在野生型中，嵴囊泡的高曲率边缘密集地填充有ATP合酶分子，所述ATP合酶分子通常组织成一排或两排二聚体。在这两个突变体中，ATP合酶的密度降低，尽管在高曲率区的表达水平不变。与野生型相比，二聚体行在突变体中较少延伸，并且二聚体的方向更分散。这些数据表明，心磷脂促进ATP合酶二聚体的带状组装，从而影响嵴膜的侧向组织和形态。
F1F0 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.