PINK1/Parkin Influences Cell Cycle by Sequestering TBK1 at Damaged Mitochondria, Inhibiting Mitosis
| Autor: | Shireen A. Sarraf, Dionisia P. Sideris, Nikolaos Giagtzoglou, Lina Ni, Mark W. Kankel, Anindya Sen, Lauren E. Bochicchio, Chiu-Hui Huang, Samuel C. Nussenzweig, Stuart H. Worley, Paul D. Morton, Spyros Artavanis-Tsakonas, Richard J. Youle, Alicia M. Pickrell |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Cell Reports, Vol 29, Iss 1, Pp 225-235.e5 (2019) |
| Druh dokumentu: | article |
| ISSN: | 2211-1247 38864797 |
| DOI: | 10.1016/j.celrep.2019.08.085 |
| Popis: | Summary: PINK1 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. : Sarraf et al. use mouse and fly genetics to discover that PINK1 and Parkin influence cell cycle progression. Mitophagy and mitosis independently activate TBK1 at damaged mitochondria and centrosomes, respectively, influencing whether the cell will address mitochondrial quality control or progress with proliferation. Keywords: PINK1, Parkin, mitosis, mitophagy, TBK1, cell cycle, ATM, centrosome, tank binding kinase 1, ik2 |
| Databáze: | Directory of Open Access Journals |
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