Selective Oma1 Protease-mediated Proteolysis of Cox1 Subunit of Cytochrome Oxidase in Assembly Mutants

Selective Oma1 Protease-mediated Proteolysis of Cox1 Subunit of Cytochrome Oxidase in Assembly Mutants
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DOI:
10.1074/jbc.m111.313148
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发表时间:
2012-03-02
影响因子:
4.8
通讯作者:
Winge, Dennis R.
Winge, Dennis R.
中科院分区:
生物学2区
文献类型:
--
作者:
Khalimonchuk, Oleh;Jeong, Mi-Young;Winge, Dennis R.

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线粒体细胞色素c氧化酶(CcO)复合物的生物合成停滞导致含有氧化还原辅因子的亚基降解。保守的Oma1金属蛋白酶介导的细胞缺乏Coa2组装因子的Cox1降解,但不是在一系列其他突变体停滞在CcO成熟。Oma1在coa2 Delta细胞中被激活,但选择性Cox1降解并不仅仅源于其激活。Oma1在线粒体功能障碍的细胞和CcO成熟受损的cox11 Delta细胞中也有活性,但这种激活不会导致Oma1介导的Cox1降解。Cox1在coa2 Delta细胞中相对于其他CcO组装突变体的简易和选择性降解可能是由于受损的半化和随后的亚基错误折叠。Coa2 Delta细胞中的特异性Cox1蛋白水解是由Oma1激活和Cox1易感构象的组合引起的。
Stalled biogenesis of the mitochondrial cytochrome c oxidase (CcO) complex results in degradation of subunits containing redox cofactors. The conserved Oma1 metalloproteinase mediates facile Cox1 degradation in cells lacking the Coa2 assembly factor, but not in a series of other mutants stalled in CcO maturation. Oma1 is activated in coa2 Delta cells, but the selective Cox1 degradation does not arise merely from its activation. Oma1 is also active in cells with dysfunctional mitochondria and cox11 Delta cells impaired in CcO maturation, but this activation does not result in Oma1-mediated Cox1 degradation. The facile and selective degradation of Cox1 in coa2 Delta cells, relative to other CcO assembly mutants, is likely due to impaired hemylation and subsequent misfolding of the subunit. Specific Cox1 proteolysis in coa2 Delta cells arises from a combination of Oma1 activation and a susceptible conformation of Cox1.