title: Cytosolic cleaved PINK1 represses Parkin translocation to mitochondria and mitophagy.
abstract: PINK1 is a mitochondrial kinase proposed to have a role in the pathogenesis of Parkinson's disease through the regulation of mitophagy. Here, we show that the PINK1 main cleavage product, PINK152, after being generated inside mitochondria, can exit these organelles and localize to the cytosol, where it is not only destined for degradation by the proteasome but binds to Parkin. The interaction of cytosolic PINK1 with Parkin represses Parkin translocation to the mitochondria and subsequent mitophagy. Our work therefore highlights the existence of two cellular pools of PINK1 that have different effects on Parkin translocation and mitophagy.
authors.affiliation: Center for Motor Neuron Biology and Disease and the Columbia Translational Neuroscience Initiative, Columbia University, New York, NY, USA.
authors.forename: Maja A
authors.initials: MA
authors.lastname: Fedorowicz
authors.forename: Rosa L A
authors.initials: RL
authors.lastname: de Vries-Schneider
authors.forename: Cornelia
authors.initials: C
authors.lastname: Rüb
authors.forename: Dorothea
authors.initials: D
authors.lastname: Becker
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Chun
authors.initials: C
authors.lastname: Zhou
authors.forename: Dana M
authors.initials: DM
authors.lastname: Alessi Wolken
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voos
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Liu
authors.forename: Serge
authors.initials: S
authors.lastname: Przedborski
mesh_terms: D003600:Cytosol / Q000201:enzymology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000201:enzymology; D063306:Mitophagy; D010300:Parkinson Disease / Q000201:enzymology; D061988:Proteasome Inhibitors / Q000494:pharmacology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011494:Protein Kinases / Q000502:physiology*; D021381:Protein Transport; D059748:Proteolysis; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014634:Valinomycin / Q000494:pharmacology; D000099202:PTEN-Induced Putative Kinase
chemical_list: D007976:Leupeptins; D061988:Proteasome Inhibitors; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D014634:Valinomycin; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde