PARK6 (PINK1) degradation
Contributor: Simone Patergnani
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Theorem
Information
The serine/threonine kinase PINK1 (PARK6) is constitutively degrade under steady-state conditions, whereas accumulates at the outer mitochondrial membrane (OMM) of damaged mitochondria to recruit Parkin and induce mitophagy. In normal (non-stressed) cells, PARK6 precursor if firstly imported inside the matrix and then cleaved by the PARL protease, which in turn induces the retrotranslocation of PARK6 to the cytosol. Here, cleaved PARK6 is recognized by the proteasome system and degraded.
References:
Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010 Jan 26;8(1):e1000298. doi: 10.1371/journal.pbio.1000298. PMID: 20126261.
Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ. Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol. 2010 Nov 29;191(5):933-42. doi: 10.1083/jcb.201008084. PMID: 21115803.
Yamano K, Youle RJ. PINK1 is degraded through the N-end rule pathway. Autophagy. 2013 Nov 1;9(11):1758-69. doi: 10.4161/auto.24633. Epub 2013 Apr 17. PMID: 24121706.
Link to other Databases:
Mitochondrial processes
Demonstrative and biological steps
Dynamic view
Mito-location
Not Available/Not Relevant
Matrix
Inner Membrane
Inter-Membrane Space
Outer Membrane
