Med13p prevents mitochondrial fission and programmed cell death in yeast through nuclear retention of cyclin C

Svetlana Khakhina, Katrina F. Cooper, Randy Strich

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


The yeast cyclin C-Cdk8 kinase forms a complex with Med13p to repress the transcription of genes involved in the stress response and meiosis. In response to oxidative stress, cyclin C displays nuclear to cytoplasmic relocalization that triggers mitochondrial fission and promotes programmed cell death. In this report, we demonstrate that Med13p mediates cyclin C nuclear retention in unstressed cells. Deleting MED13 allows aberrant cytoplasmic cyclin C localization and extensive mitochondrial fragmentation. Loss of Med13p function resulted in mitochondrial dysfunction and hypersensitivity to oxidative stress-induced programmed cell death that were dependent on cyclin C. The regulatory system controlling cyclin C-Med13p interaction is complex. First, a previous study found that cyclin C phosphorylation by the stress-activated MAP kinase Slt2p is required for nuclear to cytoplasmic translocation. This study found that cyclin C-Med13p association is impaired when the Slt2p target residue is substituted with a phosphomimetic amino acid. The second step involves Med13p destruction mediated by the 26S proteasome and cyclin C-Cdk8p kinase activity. In conclusion, Med13p maintains mitochondrial structure, function, and normal oxidative stress sensitivity through cyclin C nuclear retention. Releasing cyclin C from the nucleus involves both its phosphorylation by Slt2p coupled with Med13p destruction.

Original languageEnglish (US)
Pages (from-to)2807-2816
Number of pages10
JournalMolecular biology of the cell
Issue number18
StatePublished - Sep 15 2014

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


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