Stress-induced nuclear-to-cytoplasmic translocation of cyclin C promotes mitochondrial fission in yeast.
Mitochondrial morphology is maintained by the opposing activities of dynamin-based fission and fusion machines. In response to stress, this balance is dramatically shifted toward fission. This study reveals that the yeast transcriptional repressor cyclin C is both necessary and sufficient for stress-induced hyperfission. In response to oxidative stress, cyclin C translocates from the nucleus to the cytoplasm, where it is destroyed. Prior to its destruction, cyclin C both genetically and physically interacts with Mdv1p, an adaptor that links the GTPase Dnm1p to the mitochondrial receptor Fis1p. Cyclin C is required for stress-induced Mdv1p mitochondrial recruitment and the efficient formation of functional Dnm1p filaments. Finally, coimmunoprecipitation studies and fluorescence microscopy revealed an elevated association between Mdv1p and Dnm1p in stressed cells that is dependent on cyclin C. This study provides a mechanism by which stress-induced gene induction and mitochondrial fission are coordinated through translocation of cyclin C.
Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA.
Katrina F
KF
Cooper
Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA.
Svetlana
S
Khakhina
Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA.
Stephen K
SK
Kim
Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA. Electronic address: strichra@rowan.edu.
Randy
R
Strich
D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D056850:Cyclin-Dependent Kinase 8 / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C429283:MDV1 protein, S cerevisiae; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D056850:Cyclin-Dependent Kinase 8; C498309:SSN3 protein, S cerevisiae; D020558:GTP Phosphohydrolases; C094774:DNM1 protein, S cerevisiae