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Cell Rep. 2017 Sep 19;20(12):2846-2859. doi: 10.1016/j.celrep.2017.08.087.

Parkin-Independent Mitophagy Controls Chemotherapeutic Response in Cancer Cells.

Author information

1
Université Côte d'Azur, INSERM, C3M, Nice, France.
2
Cancer Research UK Beatson Institute, Institute of Cancer Sciences, University of Glasgow, Switchback Road, Glasgow, UK.
3
Université Côte d'Azur, INSERM, C3M, Nice, France. Electronic address: ricci@unice.fr.

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.

KEYWORDS:

ARIH1; E3 ligase; PINK1; Parkin-independent; RBR-ligase; cell death; chemoresistance; lung cancer; mitophagy; mtKeima

PMID:
28930681
DOI:
10.1016/j.celrep.2017.08.087
[Indexed for MEDLINE]
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