title: Quality control of oxidatively damaged mitochondrial proteins is mediated by p97 and the proteasome.
abstract: Protein quality control is essential for maintaining mitochondrial fidelity. Proteins damaged by reactive oxygen species necessitate quality control to prevent mitochondrial dysfunction connected to aging and neurodegeneration. Here we report a role for the AAA ATPase p97/VCP and the proteasome in the quality control of oxidized mitochondrial proteins under low oxidative stress as well as normal conditions. Proteasomal inhibition and blocking p97-dependent protein retrotranslocation interfered with degradation of oxidized mitochondrial proteins. Thus, ubiquitin-dependent, p97-, and proteasome-mediated degradation of oxidatively damaged proteins plays a key role in maintaining mitochondrial fidelity and is likely an important defense mechanism against aging and neurodegeneration.
authors: Department of Biomedicine, University Basel, Basel, Switzerland.
authors: Charles
authors: C
authors: Hemion
authors: Department of Ophthalmology, University Basel, Basel, Switzerland.
authors: Josef
authors: J
authors: Flammer
authors: Department of Biomedicine, University Basel, Basel, Switzerland; Department of Ophthalmology, University Basel, Basel, Switzerland. Electronic address: albert.neutzner@unibas.ch.
authors: Albert
authors: A
authors: Neutzner
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D016922:Cellular Senescence; D006801:Humans; D008928:Mitochondria / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000737:chemistry; D012402:Rotenone / Q000494:pharmacology; D014452:Ubiquitins / Q000378:metabolism; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D014452:Ubiquitins; D012402:Rotenone; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C404942:p97 ATPase; C000614178:VCP protein, human; D000074405:Valosin Containing Protein
keywords: Mitochondria; Proteasome; Protein quality control; Reactive oxygen species; p97