Mitochondria and cell death-associated inflammation

Vringer, E. and Tait, S. W.G. (2023) Mitochondria and cell death-associated inflammation. Cell Death and Differentiation, 30(2), pp. 304-312. (doi: 10.1038/s41418-022-01094-w) (PMID:36447047) (PMCID:PMC9950460)

Abstract

Mitochondria have recently emerged as key drivers of inflammation associated with cell death. Many of the pro-inflammatory pathways activated during cell death occur upon mitochondrial outer membrane permeabilization (MOMP), the pivotal commitment point to cell death during mitochondrial apoptosis. Permeabilised mitochondria trigger inflammation, in part, through the release of mitochondrial-derived damage-associated molecular patterns (DAMPs). Caspases, while dispensable for cell death during mitochondrial apoptosis, inhibit activation of pro-inflammatory pathways after MOMP. Some of these mitochondrial-activated inflammatory pathways can be traced back to the bacterial ancestry of mitochondria. For instance, mtDNA and bacterial DNA are highly similar thereby activating similar cell autonomous immune signalling pathways. The bacterial origin of mitochondria suggests that inflammatory pathways found in cytosol-invading bacteria may be relevant to mitochondrial-driven inflammation after MOMP. In this review, we discuss how mitochondria can initiate inflammation during cell death highlighting parallels with bacterial activation of inflammation. Moreover, we discuss the roles of mitochondrial inflammation during cell death and how these processes may potentially be harnessed therapeutically, for instance to improve cancer treatment.

• Item Type: Articles
• Additional Information: Research in our lab is supported by Cancer Research UK, Prostate Cancer UK and the Swiss National Science Foundation.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tait, Professor Stephen and Vringer, Esmee
• Authors: Vringer, E., and Tait, S. W.G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell Death and Differentiation
• Publisher: Springer Nature
• ISSN: 1350-9047
• ISSN (Online): 1476-5403
• Published Online: 29 November 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Cell Death and Differentiation 30(2): 304-312
• Publisher Policy: Reproduced under a Creative Commons License

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