PINK1/Parkin Influences Cell Cycle by Sequestering TBK1 at Damaged Mitochondria, Inhibiting Mitosis

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dc.contributor.authorSarraf, Shireen A.en
dc.contributor.authorSideris, Dionisia P.en
dc.contributor.authorGiagtzoglou, Nikolaosen
dc.contributor.authorArtavanis-Tsakonas, Spyrosen
dc.contributor.authorYoule, Richard J.en
dc.contributor.authorPickrell, Alicia M.en
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.contributor.departmentSchool of Neuroscienceen
dc.date.accessioned2020-02-03T17:44:45Zen
dc.date.available2020-02-03T17:44:45Zen
dc.date.issued2019-10-01en
dc.description.abstractPINK1 and Parkin are established mediators of mitophagy, the selective removal of damaged mitochondria by autophagy. PINK1 and Parkin have been proposed to act as tumor suppressors, as loss-of-function mutations are correlated with enhanced tumorigenesis. However, it is unclear how PINK1 and Parkin act in coordination during mitophagy to influence the cell cycle. Here we show that PINK1 and Parkin genetically interact with proteins involved in cell cycle regulation, and loss of PINK1 and Parkin accelerates cell growth. PINK1- and Parkin-mediated activation of TBK1 at the mitochondria during mitophagy leads to a block in mitosis due to the sequestration of TBK1 from its physiological role at centrosomes during mitosis. Our study supports a diverse role for the far-reaching, regulatory effects of mitochondrial quality control in cellular homeostasis and demonstrates that the PINK1/Parkin pathway genetically interacts with the cell cycle, providing a framework for understanding the molecular basis linking PINK1 and Parkin to mitosis.en
dc.description.sponsorshipThis work was supported in part by the NIH NINDS intramural program (R.J.Y., S.A.S., D.P.S., C.-H.H., and A.M.P.), departmental startup funds (A.M.P.), the Virginia Tech Open Access Subvention Fund (A.M.P.), and NIGMS Postdoctoral Research Associate Fellowships (A.M.P. and S.A.S.). We would like to thank the NINDS Microscopy Core, NHLBI Flow Cytometry Core, Dr. Chunxin Wang for technical advice and stimulating scientific conversation, and Dr. Katherine Roche for stimulating scientific conversation.en
dc.format.extent17 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSarraf et al., 2019, Cell Reports 29, 225–235 October 1, 2019 ª 2019 The Author(s). https://doi.org/10.1016/j.celrep.2019.08.085en
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2019.08.085en
dc.identifier.urihttp://hdl.handle.net/10919/96674en
dc.identifier.volume29en
dc.language.isoenen
dc.publisherCell Pressen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.titlePINK1/Parkin Influences Cell Cycle by Sequestering TBK1 at Damaged Mitochondria, Inhibiting Mitosisen
dc.title.serialCell Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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