Cell Reports (Sep 2017)

Parkin-Independent Mitophagy Controls Chemotherapeutic Response in Cancer Cells

  • Elodie Villa,
  • Emma Proïcs,
  • Camila Rubio-Patiño,
  • Sandrine Obba,
  • Barbara Zunino,
  • Jozef P. Bossowski,
  • Romain M. Rozier,
  • Johanna Chiche,
  • Laura Mondragón,
  • Joel S. Riley,
  • Sandrine Marchetti,
  • Els Verhoeyen,
  • Stephen W.G. Tait,
  • Jean-Ehrland Ricci

DOI
https://doi.org/10.1016/j.celrep.2017.08.087
Journal volume & issue
Vol. 20, no. 12
pp. 2846 – 2859

Abstract

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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.

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