A LON-ClpP Proteolytic Axis Degrades Complex I to Extinguish ROS Production in Depolarized Mitochondria

• DOI: 10.1016/j.celrep.2016.11.027
• Publication Date: 2016-12-06T18:16:43Z
• Authors: Kenneth Robert Pryde; Jan Willem Taanman; Anthony Henry Sch...
• Keywords: Proteolysis; Proteolytic enzymes

Mitochondrial dysfunction is implicated in numerous neurodegenerative disorders and Parkinson's disease (PD) particular. PINK1 Parkin gene mutations are causes of autosomal recessive PD, these respective proteins function cooperatively to degrade depolarized mitochondria (mitophagy). It widely assumed that impaired mitophagy as toxic reactive oxygen species (ROS)-producing accumulate progressively drive neurodegeneration. Instead, we report a LON-ClpP proteolytic quality control axis extinguishes ROS by degrading the complex I ROS-generating domain. Complex deficiency has also been identified PD brain, our study provides compelling non-genetic mechanistic rationale explain this observation: intact depletes if mitochondrial bioenergetic capacity robustly attenuated.