Detailed analysis of the human mitochondrial contact site complex indicate a hierarchy of subunits.

Detailed analysis of the human mitochondrial contact site complex indicate a hierarchy of subunits.
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DOI:
10.1371/journal.pone.0120213
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Kozjak-Pavlovic V
Kozjak-Pavlovic V
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ott C;Dorsch E;Fraunholz M;Straub S;Kozjak-Pavlovic V

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线粒体内膜折叠成嵴,这显著增加了它的表面,对线粒体功能很重要。嵴的稳定性依赖于线粒体接触位点复合体。在人类线粒体中,内膜MICOS复合物与外膜分选和组装机械(SAM)复合物相互作用,以形成线粒体膜间空间桥接复合物(MIB)。我们已经建立了大多数MICOS和MIB组分的敲低细胞系,并使用它们来研究单个亚基对嵴形成和复合物稳定性的重要性。我们发现,在人类线粒体中的MIB复合物的最重要的亚基是Mic 60/Mitofilin,Mic 19/CHCHD 3和外膜组件Sam 50。我们提供了额外的证据,ApoO确实是一个亚基的MICOS和MIB复合物,并提出了名称Mic 23这种蛋白质。根据我们的结果,Mic 25/CHCHD 6,Mic 27/ApoOL和Mic 23/ApoO似乎是MICOS复合物的外围亚基,因为它们的缺失不影响嵴形态或其他组分的稳定性。
Mitochondrial inner membrane folds into cristae, which significantly increase its surface and are important for mitochondrial function. The stability of cristae depends on the mitochondrial contact site (MICOS) complex. In human mitochondria, the inner membrane MICOS complex interacts with the outer membrane sorting and assembly machinery (SAM) complex, to form the mitochondrial intermembrane space bridging complex (MIB). We have created knockdown cell lines of most of the MICOS and MIB components and have used them to study the importance of the individual subunits for the cristae formation and complex stability. We show that the most important subunits of the MIB complex in human mitochondria are Mic60/Mitofilin, Mic19/CHCHD3 and an outer membrane component Sam50. We provide additional proof that ApoO indeed is a subunit of the MICOS and MIB complexes and propose the name Mic23 for this protein. According to our results, Mic25/CHCHD6, Mic27/ApoOL and Mic23/ApoO appear to be periphery subunits of the MICOS complex, because their depletion does not affect cristae morphology or stability of other components.
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