Mitochondria as multifaceted regulators of cell death

Bock, F. J. and Tait, S. W.G. (2020) Mitochondria as multifaceted regulators of cell death. Nature Reviews Molecular Cell Biology, 21, pp. 85-100. (doi: 10.1038/s41580-019-0173-8) (PMID:31636403)

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Abstract

Through their many and varied metabolic functions, mitochondria power life. Paradoxically, mitochondria also have a central role in apoptotic cell death. Upon induction of mitochondrial apoptosis, mitochondrial outer membrane permeabilization (MOMP) usually commits a cell to die. Apoptotic signalling downstream of MOMP involves cytochrome c release from mitochondria and subsequent caspase activation. As such, targeting MOMP in order to manipulate cell death holds tremendous therapeutic potential across different diseases, including neurodegenerative diseases, autoimmune disorders and cancer. In this Review, we discuss new insights into how mitochondria regulate apoptotic cell death. Surprisingly, recent data demonstrate that besides eliciting caspase activation, MOMP engages various pro-inflammatory signalling functions. As we highlight, together with new findings demonstrating cell survival following MOMP, this pro-inflammatory role suggests that mitochondria-derived signalling downstream of pro-apoptotic cues may also have non-lethal functions. Finally, we discuss the importance and roles of mitochondria in other forms of regulated cell death, including necroptosis, ferroptosis and pyroptosis. Collectively, these new findings offer exciting, unexplored opportunities to target mitochondrial regulation of cell death for clinical benefit.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tait, Professor Stephen and Bock, Dr Florian
Authors: Bock, F. J., and Tait, S. W.G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Nature Reviews Molecular Cell Biology
Publisher:Nature Publishing Group
ISSN:1471-0072
ISSN (Online):1471-0080
Published Online:21 October 2019
Copyright Holders:Copyright © 2019 Springer Nature
First Published:First published in Nature Reviews Molecular Cell Biology 21:85-100
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172007Apoptosis as an oncogenic process: understanding and exploiting its dark-sideStephen TaitCancer Research UK (CRUK)C40872/A20145Institute of Cancer Sciences
301861Targeting immunogenic cell death to treat prostate cancerStephen TaitProstate Cancer UK (PROSCANU)RIA17-ST2-002CS - Beatson Institute for Cancer Research