USP30 deubiquitylates mitochondrial Parkin substrates and restricts apoptotic cell death

Jin Rui Liang; Aitor Martinez; Jon D. Lane; Ugo Mayor; Michael J. Clague; Sylvie Urbé

doi:10.15252/embr.201439820

USP30 deubiquitylates mitochondrial Parkin substrates and restricts apoptotic cell death

Jin Rui Liang
, Aitor Martinez
, Jon D. Lane
, Ugo Mayor
, Michael J. Clague (Lead / Corresponding author)
, Sylvie Urbé (Lead / Corresponding author)

MRC PPU

Research output: Contribution to journal › Article › peer-review

154 Citations (Scopus)

88 Downloads (Pure)

Abstract

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, USP30, opposes Parkin-dependent ubiquitylation of TOM20, and its depletion enhances depolarization-induced cell death in Parkin-overexpressing cells. Importantly, USP30 also regulates BAX/BAK-dependent apoptosis, and its depletion sensitizes cancer cells to BH3-mimetics. These results provide the first evidence for a fundamental role of USP30 in determining the threshold for mitochondrial cell death and suggest USP30 as a potential target for combinatorial anti-cancer therapy.

Original language	English
Pages (from-to)	618-627
Number of pages	10
Journal	EMBO Reports
Volume	16
Issue number	5
Early online date	4 Mar 2015
DOIs	https://doi.org/10.15252/embr.201439820
Publication status	Published - 1 May 2015

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

apoptosis
mitophagy
Parkin
TOM20
USP30

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics

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10.15252/embr.201439820Licence: CC BY

Final published versionFinal published version, 2.45 MBLicence: CC BY

Cite this

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title = "USP30 deubiquitylates mitochondrial Parkin substrates and restricts apoptotic cell death",

abstract = "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, USP30, opposes Parkin-dependent ubiquitylation of TOM20, and its depletion enhances depolarization-induced cell death in Parkin-overexpressing cells. Importantly, USP30 also regulates BAX/BAK-dependent apoptosis, and its depletion sensitizes cancer cells to BH3-mimetics. These results provide the first evidence for a fundamental role of USP30 in determining the threshold for mitochondrial cell death and suggest USP30 as a potential target for combinatorial anti-cancer therapy.",

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author = "Liang, \{Jin Rui\} and Aitor Martinez and Lane, \{Jon D.\} and Ugo Mayor and Clague, \{Michael J.\} and Sylvie Urb{\'e}",

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doi = "10.15252/embr.201439820",

language = "English",

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TY - JOUR

T1 - USP30 deubiquitylates mitochondrial Parkin substrates and restricts apoptotic cell death

AU - Liang, Jin Rui

AU - Martinez, Aitor

AU - Lane, Jon D.

AU - Mayor, Ugo

AU - Clague, Michael J.

AU - Urbé, Sylvie

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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, USP30, opposes Parkin-dependent ubiquitylation of TOM20, and its depletion enhances depolarization-induced cell death in Parkin-overexpressing cells. Importantly, USP30 also regulates BAX/BAK-dependent apoptosis, and its depletion sensitizes cancer cells to BH3-mimetics. These results provide the first evidence for a fundamental role of USP30 in determining the threshold for mitochondrial cell death and suggest USP30 as a potential target for combinatorial anti-cancer therapy.

AB - 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, USP30, opposes Parkin-dependent ubiquitylation of TOM20, and its depletion enhances depolarization-induced cell death in Parkin-overexpressing cells. Importantly, USP30 also regulates BAX/BAK-dependent apoptosis, and its depletion sensitizes cancer cells to BH3-mimetics. These results provide the first evidence for a fundamental role of USP30 in determining the threshold for mitochondrial cell death and suggest USP30 as a potential target for combinatorial anti-cancer therapy.

KW - apoptosis

KW - mitophagy

KW - Parkin

KW - TOM20

KW - USP30

UR - https://www.scopus.com/pages/publications/84928924502

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DO - 10.15252/embr.201439820

M3 - Article

C2 - 25739811

AN - SCOPUS:84928924502

SN - 1469-221X

VL - 16

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JO - EMBO Reports

JF - EMBO Reports

IS - 5

ER -

USP30 deubiquitylates mitochondrial Parkin substrates and restricts apoptotic cell death

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

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