C11orf83, a Mitochondrial Cardiolipin-Binding Protein Involved in bc1 Complex Assembly and Supercomplex Stabilization
C11orf83, a Mitochondrial Cardiolipin-Binding Protein Involved in bc1 Complex Assembly and Supercomplex Stabilization
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DOI：
10.1128/mcb.01047-14
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发表时间：
2015-04-01
影响因子：
5.3
通讯作者：
Lane, Lydie
中科院分区：
文献类型：
--
作者：
Desmurs, Marjorie;Foti, Michelangelo;Lane, Lydie
哺乳动物线粒体可能包含多达1500种不同的蛋白质，其中许多还没有被确定或表征。在本研究中，我们证明了C11orf83是一种面向膜间隙的线粒体内膜蛋白，但缺乏实验特性。该蛋白与电子传输链的BC(1)复合体特异性结合，并通过稳定BC(1)核心复合体参与其组装的早期阶段。C11orf83与酵母BC(1)复合组装因子Cbp4p具有重叠功能。因此，我们认为C11orf83，现在被称为UQCC3，是人类功能等价物Cbp4p。此外，HeLa细胞中C11orf83的缺失导致了异常的晶体形态，对凋亡的敏感性更高，由于呼吸障碍而导致的ATP水平下降，以及心磷脂成分的轻微但显著的变化。我们发现C11orf83通过其α-螺旋2和3与心磷脂结合，并参与含BC(1)超络合物，特别是III2/IV超络合物的稳定。我们还证明了OMA1金属蛋白酶在线粒体去极化的反应中裂解C11orf83，这表明在选择线粒体受损的细胞以便随后通过凋亡消除它们的过程中发挥了作用，就像之前对OPA1所描述的那样。
Mammalian mitochondria may contain up to 1,500 different proteins, and many of them have neither been confidently identified nor characterized. In this study, we demonstrated that C11orf83, which was lacking experimental characterization, is a mitochondrial inner membrane protein facing the intermembrane space. This protein is specifically associated with the bc(1) complex of the electron transport chain and involved in the early stages of its assembly by stabilizing the bc(1) core complex. C11orf83 displays some overlapping functions with Cbp4p, a yeast bc(1) complex assembly factor. Therefore, we suggest that C11orf83, now called UQCC3, is the functional human equivalent of Cbp4p. In addition, C11orf83 depletion in HeLa cells caused abnormal crista morphology, higher sensitivity to apoptosis, a decreased ATP level due to impaired respiration and subtle, but significant, changes in cardiolipin composition. We showed that C11orf83 binds to cardiolipin by its alpha-helices 2 and 3 and is involved in the stabilization of bc(1) complex-containing supercomplexes, especially the III2/IV supercomplex. We also demonstrated that the OMA1 metalloprotease cleaves C11orf83 in response to mitochondrial depolarization, suggesting a role in the selection of cells with damaged mitochondria for their subsequent elimination by apoptosis, as previously described for OPA1.