Deciphering the Molecular Signals of PINK1/Parkin Mitophagy.
Functional mitochondria are critically important for the maintenance of cellular integrity and survival. Mitochondrial dysfunction is a major contributor to neurodegenerative diseases including Parkinson's disease (PD). Two gene products mutated in familial Parkinsonism, PINK1 and Parkin, function together to degrade damaged mitochondria through a selective form of autophagy termed mitophagy. PINK1 accumulates on the surface of dysfunctional mitochondria where it simultaneously recruits and activates Parkin's E3 ubiquitin ligase activity. This forms the basis of multiple signaling events that culminate in engulfment of damaged mitochondria within autophagosomes and degradation by lysosomes. This review discusses the molecular signals of PINK1/Parkin mitophagy and the ubiquitin code that drives not only Parkin recruitment and activation by PINK1 but also the downstream signaling events of mitophagy.
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Australia.
Thanh N
TN
Nguyen
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Australia.
Benjamin S
BS
Padman
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Australia. Electronic address: Michael.Lazarou@Monash.edu.
Michael
M
Lazarou
D000818:Animals; D000071182:Autophagosomes / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D063306:Mitophagy; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein
PINK1; Parkin; Parkinson's disease; autophagy; mitophagy; ubiquitin