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Parkin structure and function
Author(s) -
Seirafi Marjan,
Kozlov Guennadi,
Gehring Kalle
Publication year - 2015
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13249
Subject(s) - parkin , mitophagy , pink1 , ubiquitin ligase , ubiquitin , microbiology and biotechnology , biology , autophagy , neuroprotection , mitochondrion , drug discovery , parkinson's disease , ubiquitin protein ligases , genetics , gene , biochemistry , pharmacology , disease , medicine , apoptosis , pathology
Mutations in the parkin or PINK 1 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 PINK 1, 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.