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USP 30 deubiquitylates mitochondrial P arkin substrates and restricts apoptotic cell death
Author(s) -
Liang JinRui,
Martinez Aitor,
Lane Jon D,
Mayor Ugo,
Clague Michael J,
Urbé Sylvie
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201439820
Subject(s) - microbiology and biotechnology , programmed cell death , apoptosis , mitochondrion , parkin , ubiquitin , biology , cell , ubiquitin ligase , depolarization , cancer cell , chemistry , cancer , genetics , biophysics , medicine , disease , pathology , parkinson's disease , gene
Mitochondria play a pivotal role in the orchestration of cell death pathways. Here, we show that the control of ubiquitin dynamics at mitochondria contributes to the regulation of apoptotic cell death. The unique mitochondrial deubiquitylase, USP 30, opposes Parkin‐dependent ubiquitylation of TOM 20, and its depletion enhances depolarization‐induced cell death in Parkin‐overexpressing cells. Importantly, USP 30 also regulates BAX / BAK ‐dependent apoptosis, and its depletion sensitizes cancer cells to BH 3‐mimetics. These results provide the first evidence for a fundamental role of USP 30 in determining the threshold for mitochondrial cell death and suggest USP 30 as a potential target for combinatorial anti‐cancer therapy.