Parkin-independent mitophagy controls chemotherapeutic response in cancer cells

Villa, E. et al. (2017) Parkin-independent mitophagy controls chemotherapeutic response in cancer cells. Cell Reports, 20(12), pp. 2846-2859. (doi:10.1016/j.celrep.2017.08.087) (PMID:28930681)

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Abstract

Mitophagy is an evolutionarily conserved process that selectively targets impaired mitochondria for degradation. Defects in mitophagy are often associated with diverse pathologies, including cancer. Because the main known regulators of mitophagy are frequently inactivated in cancer cells, the mechanisms that regulate mitophagy in cancer cells are not fully understood. Here, we identified an E3 ubiquitin ligase (ARIH1/HHARI) that triggers mitophagy in cancer cells in a PINK1-dependent manner. We found that ARIH1/HHARI polyubiquitinates damaged mitochondria, leading to their removal via autophagy. Importantly, ARIH1 is widely expressed in cancer cells, notably in breast and lung adenocarcinomas; ARIH1 expression protects against chemotherapy-induced death. These data challenge the view that the main regulators of mitophagy are tumor suppressors, arguing instead that ARIH1-mediated mitophagy promotes therapeutic resistance.

Item Type:Articles
Additional Information:We thank Conseil General des AM et de la region PACA et Corse for their financial support. This work was supported by the Fondation ARC (Association pour la Recherche sur le Cancer) and the Agence Nationale de la Recherche (LABEX SIGNALIFE ANR-11-LABX-0028-01). E.V. is supported by La Ligue contre le Cancer. C.R.-P. is supported by the Fondation ARC and J.C. by Foundation Tourre. L.M and S.O. were supported by la Fondation pour la Recherche Me´ dicale (FRM)
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Riley, Dr Joel and Tait, Professor Stephen
Authors: Villa, E., Proïcs, E., Rubio-Patiño, C., Obba, S., Zunino, B., Bossowski, J. P., Rozier, R. M., Chiche, J., Mondragón, L., Riley, J. S., Marchetti, S., Verhoeyen, E., Tait, S. W.G., and Ricci, J.-E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cell Reports
Publisher:Elsevier (Cell Press)
ISSN:2211-1247
ISSN (Online):2211-1247
Published Online:19 September 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Cell Reports 20(12):2846-2859
Publisher Policy:Reproduced under a Creative Commons License

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