Premium
The intracellular redox state is a core determinant of mitochondrial fusion
Author(s) -
Shutt Timothy,
Geoffrion Michèle,
Milne Ross,
McBride Heidi M
Publication year - 2012
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2012.128
Subject(s) - mitophagy , mitochondrial fusion , microbiology and biotechnology , mitochondrion , glutathione , oxidative stress , intracellular , fusion , biology , mitochondrial fission , biochemistry , chemistry , biophysics , apoptosis , mitochondrial dna , autophagy , gene , linguistics , philosophy , enzyme
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.