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)

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 > School 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172007		Apoptosis as an oncogenic process: understanding and exploiting its dark-side	Stephen Tait	Cancer Research UK (CRUK)	C40872/A20145	Institute of Cancer Sciences
301861		Targeting immunogenic cell death to treat prostate cancer	Stephen Tait	Prostate Cancer UK (PROSCANU)	RIA17-ST2-002	CS - Beatson Institute for Cancer Research