Functional TIM10 chaperone assembly is redox-regulated in vivo

被引:101
作者
Lu, H
Allen, S
Wardleworth, L
Savory, P
Tokatlidis, K
机构
[1] Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England
[2] Univ Crete, Dept Chem, Iraklion 71409, Greece
[3] FORTH, IMBB, Iraklion 71110, Greece
基金
英国医学研究理事会;
关键词
D O I
10.1074/jbc.M313045200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The TIM10 chaperone facilitates the insertion of hydrophobic proteins at the mitochondrial inner membrane. Here we report the novel molecular mechanism of TIM10 assembly. This process crucially depends on oxidative folding in mitochondria and involves: (i) import of the subunits in a Cys-reduced and unfolded state; (ii) folding to an assembly-competent structure maintained by intramolecular disulfide bonding of their four conserved cysteines; and (iii) assembly of the oxidized zinc-devoid subunits to the functional complex. We show that intramolecular disulfide bonding occurs in vivo, whereas intermolecular disulfides observed in vitro are abortive intermediates in the assembly pathway. This novel mechanism of compartment-specific redox-regulated assembly is crucial for the formation of a functional TIM10 chaperone.
引用
收藏
页码:18952 / 18958
页数:7
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