Parkin structure and function

• Published in: The FEBS journal Vol. 282; no. 11; pp. 2076 - 2088
• Main Authors: Seirafi, Marjan, Kozlov, Guennadi, Gehring, Kalle
• Format: Journal Article
• Language: English
• Published: England Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies 01.06.2015; Blackwell Publishing Ltd; John Wiley & Sons, Ltd
• Subjects: Amino Acid Sequence; Animals; autophagy; drugs; genes; Humans; mitochondria; Mitochondria - enzymology; Mitochondrial Degradation; mitophagy; Molecular Sequence Data; Mutation; Neurons - enzymology; parkin; Parkinson disease; Parkinson Disease - enzymology; Parkinson Disease - pathology; PINK1; Protein Transport; protein-serine-threonine kinases; proteins; Quality control; serine; State-of-the-Art Review; threonine; ubiquitin; ubiquitin-protein ligase; Ubiquitin-Protein Ligases - chemistry; Ubiquitin-Protein Ligases - physiology; Ubiquitination; PINK1; mitophagy; parkin; ubiquitination; ubiquitin
• ISSN: 1742-464X; 1742-4658; 1742-4658
• DOI: 10.1111/febs.13249

Mutations in the parkin or PINK1 genes are the leading cause of the autosomal recessive form of Parkinson's disease. The gene products, the E3 ubiquitin ligase parkin and the serine/threonine kinase PINK1, are neuroprotective proteins, which act together in a mitochondrial quality control pathway. Here, we review the structure of parkin and mechanisms of its autoinhibition and function as a ubiquitin ligase. We present a model for the recruitment and activation of parkin as a key regulatory step in the clearance of depolarized or damaged mitochondria by autophagy (mitophagy). We conclude with a brief overview of other functions of parkin and considerations for drug discovery in the mitochondrial quality control pathway.