Cytosolic cleaved PINK 1 represses P arkin translocation to mitochondria and mitophagy
Copyright policy )Cytosolic cleaved PINK 1 represses P arkin translocation to mitochondria and mitophagy
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.
- Columbia University United States
- Icahn School of Medicine at Mount Sinai United States
- King’s University United States
- New York University United States
- University of Bonn Germany
Valinomycin, Leupeptins, Ubiquitin-Protein Ligases, Mitophagy, Parkinson Disease, Mitochondria, Protein Transport, Cytosol, HEK293 Cells, Mitochondrial Membranes, Proteolysis, Humans, Protein Interaction Domains and Motifs, Proteasome Inhibitors, Protein Kinases, HeLa Cells, Protein Binding
Valinomycin, Leupeptins, Ubiquitin-Protein Ligases, Mitophagy, Parkinson Disease, Mitochondria, Protein Transport, Cytosol, HEK293 Cells, Mitochondrial Membranes, Proteolysis, Humans, Protein Interaction Domains and Motifs, Proteasome Inhibitors, Protein Kinases, HeLa Cells, Protein Binding
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