The intracellular redox state is a core determinant of mitochondrial fusion
The intracellular redox state is a core determinant of mitochondrial fusion
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DOI：
10.1038/embor.2012.128
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发表时间：
2012-10-01
期刊：
影响因子：
7.7
通讯作者：
McBride, Heidi M.
中科院分区：
文献类型：
--
作者：
Shutt, Timothy;Geoffrion, Michele;McBride, Heidi M.
线粒体过度融合最近被证明是一种细胞应激反应，对细胞凋亡和线粒体自噬提供瞬时保护。然而，介导这种反应的机制仍然知之甚少。在这项研究中，我们证明，氧化型谷胱甘肽（GSSG），核心细胞应激指标，强烈诱导线粒体融合。生物化学和功能实验表明，GSSG诱导二硫化物介导的丝裂融合素寡聚体的产生，在一个过程中，也需要GTP水解。我们的数据概述了引发融合机制的分子事件，为线粒体融合与细胞应激反应的耦合提供了新的见解。
Mitochondrial hyperfusion has recently been shown to function as a cellular stress response, providing transient protection against apoptosis and mitophagy. However, the mechanisms that mediate this response remain poorly understood. In this study, we demonstrate that oxidized glutathione (GSSG), the core cellular stress indicator, strongly induces mitochondrial fusion. Biochemical and functional experiments show that GSSG induces the generation of disulphide-mediated mitofusin oligomers, in a process that also requires GTP hydrolysis. Our data outline the molecular events that prime the fusion machinery, providing new insights into the coupling of mitochondrial fusion with the cellular stress response.