The cristae modulator Optic atrophy 1 requires mitochondrial ATP synthase oligomers to safeguard mitochondrial function.
The cristae modulator Optic atrophy 1 requires mitochondrial ATP synthase oligomers to safeguard mitochondrial function.
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DOI：
10.1038/s41467-018-05655-x
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发表时间：
2018-08-24
影响因子：
16.6
通讯作者：
Scorrano L
中科院分区：
文献类型：
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作者：
Quintana-Cabrera R;Quirin C;Glytsou C;Corrado M;Urbani A;Pellattiero A;Calvo E;Vázquez J;Enríquez JA;Gerle C;Soriano ME;Bernardi P;Scorrano L
目前尚不清楚线粒体融合蛋白Optic atrophy 1 （OPA1）是如何抑制嵴重塑，防止线粒体功能障碍的。在这里，我们确定线粒体F1Fo-ATP合成酶是OPA1在线粒体保护中的效应器。在OPA1过表达的细胞中，由呼吸链复合物III抑制引起的质子电化学梯度的损失被钝化，这种保护被ATP合成酶抑制剂寡霉素所消除。从机制上讲，OPA1与ATP合成酶可以相互作用，但重组的OPA1不能促进脂质体中重组的纯化ATP合成酶的寡聚化，表明OPA1通过调节冠状结构促进ATP合成酶的寡聚化和逆转活性。当ATP合成酶低聚物通过沉默关键二聚化亚基e而在遗传上不稳定时，OPA1不再能够在复合物III抑制下保持线粒体功能和细胞活力。因此，OPA1通过稳定嵴形状和促进ATP合成酶寡聚来保护线粒体免受呼吸链抑制。线粒体嵴形状影响细胞凋亡和呼吸作用。本文作者表明，线粒体融合蛋白OPA1通过促进ATP合成酶寡聚和逆转活性来保护线粒体免受功能障碍。
It is unclear how the mitochondrial fusion protein Optic atrophy 1 (OPA1), which inhibits cristae remodeling, protects from mitochondrial dysfunction. Here we identify the mitochondrial F1Fo-ATP synthase as the effector of OPA1 in mitochondrial protection. In OPA1 overexpressing cells, the loss of proton electrochemical gradient caused by respiratory chain complex III inhibition is blunted and this protection is abolished by the ATP synthase inhibitor oligomycin. Mechanistically, OPA1 and ATP synthase can interact, but recombinant OPA1 fails to promote oligomerization of purified ATP synthase reconstituted in liposomes, suggesting that OPA1 favors ATP synthase oligomerization and reversal activity by modulating cristae shape. When ATP synthase oligomers are genetically destabilized by silencing the key dimerization subunit e, OPA1 is no longer able to preserve mitochondrial function and cell viability upon complex III inhibition. Thus, OPA1 protects mitochondria from respiratory chain inhibition by stabilizing cristae shape and favoring ATP synthase oligomerization. Mitochondrial cristae shape influences apoptosis and respiration. Here the authors show that the mitochondrial fusion protein OPA1 protects mitochondria from dysfunction by promoting ATP synthase oligomerization and reversal activity.
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影响因子：
64.5
作者：
Chen H;Vermulst M;Wang YE;Chomyn A;Prolla TA;McCaffery JM;Chan DC
通讯作者：
Chan DC
影响因子：
29
作者：
Civiletto G;Varanita T;Cerutti R;Gorletta T;Barbaro S;Marchet S;Lamperti C;Viscomi C;Scorrano L;Zeviani M
通讯作者：
Zeviani M
影响因子：
4.8
作者：
Bornhoevd, Carsten;Vogel, Frank;Reichert, Andreas S.
通讯作者：
Reichert, Andreas S.
DOI：
10.1046/j.1432-1327.1999.00345.x
发表时间：
1999-06-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Boyle, GM;Roucou, X;Prescott, M
通讯作者：
Prescott, M
影响因子：
12.4
作者：
通讯作者：
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