Mechanisms of mitophagy: PINK1, Parkin, USP30 and beyond.
Mitochondrial quality control is central for maintaining a healthy population of mitochondria. Two Parkinson's disease genes, mitochondrial kinase PINK1 and ubiquitin ligase Parkin, degrade damaged mitochondria though mitophagy. In this pathway, PINK1 senses mitochondrial damage and activates Parkin by phosphorylating Parkin and ubiquitin. Activated Parkin then builds ubiquitin chains on damaged mitochondria to tag them for degradation in lysosomes. USP30 deubiquitinase acts as a brake on mitophagy by opposing Parkin-mediated ubiquitination. Human genetic data point to a role for mitophagy defects in neurodegenerative diseases. This review highlights the molecular mechanisms of the mitophagy pathway and the recent advances in the understanding of mitophagy in vivo.
Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA. Electronic address: bingol.baris@gene.com.
Baris
B
Bingol
Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA.
Morgan
M
Sheng
D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism* / Q000502:physiology; D063306:Mitophagy; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology; D011494:Protein Kinases / Q000378:metabolism* / Q000502:physiology; D013869:Thiolester Hydrolases / Q000378:metabolism* / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism* / Q000502:physiology; D000099202:PTEN-Induced Putative Kinase
D024101:Mitochondrial Proteins; D011494:Protein Kinases; D013869:Thiolester Hydrolases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C532819:Usp30 protein, human; C111567:parkin protein
Mitophagy; PINK1; Parkin; Parkinson's Disease; USP30