The intracellular redox state is a core determinant of mitochondrial fusion

T Shutt, M Geoffrion, R Milne, HM McBride - EMBO reports, 2012 - embopress.org
T Shutt, M Geoffrion, R Milne, HM McBride
EMBO reports, 2012embopress.org
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 …
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.
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