title: The intracellular redox state is a core determinant of mitochondrial fusion.
abstract: 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.
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Timothy
authors.initials: T
authors.lastname: Shutt
authors.forename: Michèle
authors.initials: M
authors.lastname: Geoffrion
authors.forename: Ross
authors.initials: R
authors.lastname: Milne
authors.forename: Heidi M
authors.initials: HM
authors.lastname: McBride
mesh_terms: D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress
chemical_list: D024101:Mitochondrial Proteins; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; D019803:Glutathione Disulfide