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A stress-responsive system for mitochondrial protein degradation.

Molecular cell | Nov 12, 2010

We show that Ydr049 (renamed VCP/Cdc48-associated mitochondrial stress-responsive--Vms1), a member of an unstudied pan-eukaryotic protein family, translocates from the cytosol to mitochondria upon mitochondrial stress. Cells lacking Vms1 show progressive mitochondrial failure, hypersensitivity to oxidative stress, and decreased chronological life span. Both yeast and mammalian Vms1 stably interact with Cdc48/VCP/p97, a component of the ubiquitin/proteasome system with a well-defined role in endoplasmic reticulum-associated protein degradation (ERAD), wherein misfolded ER proteins are degraded in the cytosol. We show that oxidative stress triggers mitochondrial localization of Cdc48 and this is dependent on Vms1. When this system is impaired by mutation of Vms1, ubiquitin-dependent mitochondrial protein degradation, mitochondrial respiratory function, and cell viability are compromised. We demonstrate that Vms1 is a required component of an evolutionarily conserved system for mitochondrial protein degradation, which is necessary to maintain mitochondrial, cellular, and organismal viability.

Pubmed ID: 21070972 RIS Download

Mesh terms: Adenosine Triphosphatases | Amino Acid Sequence | Animals | Caenorhabditis elegans | Caenorhabditis elegans Proteins | Cell Cycle Proteins | Gene Deletion | Humans | Hydrogen Peroxide | Longevity | Mice | Microbial Viability | Mitochondria | Mitochondrial Proteins | Molecular Sequence Data | Protein Binding | Protein Processing, Post-Translational | Protein Transport | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins | Sirolimus | Stress, Physiological | Ubiquitin

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Associated grants

  • Agency: NIDDK NIH HHS, Id: DK071962
  • Agency: NIGMS NIH HHS, Id: GM75061
  • Agency: NIDDK NIH HHS, Id: R01 DK070149
  • Agency: NIDDK NIH HHS, Id: R56 DK071962
  • Agency: NIDDK NIH HHS, Id: DK070149
  • Agency: NIGMS NIH HHS, Id: R01 GM087346
  • Agency: NIGMS NIH HHS, Id: R01 GM087346-03
  • Agency: NIGMS NIH HHS, Id: R01 GM075061
  • Agency: NIDDK NIH HHS, Id: R01 DK071962
  • Agency: NIAMS NIH HHS, Id: K99 AR059190
  • Agency: NIGMS NIH HHS, Id: R01 GM067945
  • Agency: NIGMS NIH HHS, Id: GM087346

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