title: Cytosolic PTEN-induced Putative Kinase 1 Is Stabilized by the NF-κB Pathway and Promotes Non-selective Mitophagy.
abstract: The potential cellular function of the 53-kDa cytosolic form of PINK1 (PINK1-53) is often overlooked because of its rapid degradation by the proteasome upon its production. Although a number of recent studies have suggested various roles for PINK1-53, how this labile PINK1 species attains an adequate expression level to fulfil these roles remains unclear. Here we demonstrated that PINK1-53 is stabilized in the presence of enhanced Lys-63-linked ubiquitination and identified TRAF6-related NF-κB activation as a novel pathway involved in this. We further showed that a mimetic of PINK1-53 promotes mitophagy but, curiously, in apparently healthy mitochondria. We speculate that this "non-selective" form of mitophagy may potentially help to counteract the build-up of reactive oxygen species in cells undergoing oxidative stress and, as such, represent a cytoprotective response.
authors.affiliation: From the Neurodegeneration Research Laboratory, National Neuroscience Institute, Singapore, the Department of Physiology.
authors.forename: Grace G Y
authors.initials: GG
authors.lastname: Lim
authors.affiliation: From the Neurodegeneration Research Laboratory, National Neuroscience Institute, Singapore, the Department of Physiology, National University of Singapore, Graduate School for Integrative Sciences and Engineering, National University of Singapore, and.
authors.forename: Doreen S K
authors.initials: DS
authors.lastname: Chua
authors.affiliation: From the Neurodegeneration Research Laboratory, National Neuroscience Institute, Singapore.
authors.forename: Adeline H
authors.initials: AH
authors.lastname: Basil
authors.affiliation: From the Neurodegeneration Research Laboratory, National Neuroscience Institute, Singapore.
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Chan
authors.affiliation: From the Neurodegeneration Research Laboratory, National Neuroscience Institute, Singapore.
authors.forename: Chou
authors.initials: C
authors.lastname: Chai
authors.affiliation: the Department of Physiology.
authors.forename: Thiruma
authors.initials: T
authors.lastname: Arumugam
authors.affiliation: From the Neurodegeneration Research Laboratory, National Neuroscience Institute, Singapore, the Department of Physiology, National University of Singapore, Graduate School for Integrative Sciences and Engineering, National University of Singapore, and the Duke-National University of Singapore Graduate Medical School, Singapore Kah_Leong_Lim@nni.com.sg phslkl@nus.edu.sg.
authors.forename: Kah-Leong
authors.initials: KL
authors.lastname: Lim
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D003600:Cytosol / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D063306:Mitophagy; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination; D000099202:PTEN-Induced Putative Kinase
chemical_list: D016328:NF-kappa B; D011494:Protein Kinases; D048029:TNF Receptor-Associated Factor 6; D000099202:PTEN-Induced Putative Kinase
keywords: PTEN-induced putative kinase 1 (PINK1); Parkinson disease; mitophagy; parkin; ubiquitylation (ubiquitination)