Quality control of oxidatively damaged mitochondrial proteins is mediated by p97 and the proteasome

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.