Exposure of the inner mitochondrial membrane triggers apoptotic mitophagy.

Autor: Saunders TL; Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia. saunders.t@wehi.edu.au.; Ubiquitin Signalling Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia. saunders.t@wehi.edu.au.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia. saunders.t@wehi.edu.au., Windley SP; Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia., Gervinskas G; Monash Ramaciotti Centre for Cryo Electron Microscopy, Monash University, Melbourne, VIC, Australia., Balka KR; Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.; Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia., Rowe C; Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia., Lane R; Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.; Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia., Tailler M; Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia., Nguyen TN; Ubiquitin Signalling Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.; Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia., Ramm G; Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.; Monash Ramaciotti Centre for Cryo Electron Microscopy, Monash University, Melbourne, VIC, Australia., Lazarou M; Ubiquitin Signalling Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.; Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia., De Nardo D; Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.; Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia., Kile BT; Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.; Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia.; Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia., McArthur K; Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia. kate.mcarthur@monash.edu.; Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia. kate.mcarthur@monash.edu.
Jazyk: angličtina
Zdroj: Cell death and differentiation [Cell Death Differ] 2024 Mar; Vol. 31 (3), pp. 335-347. Date of Electronic Publication: 2024 Feb 23.
DOI: 10.1038/s41418-024-01260-2
Abstrakt: During apoptosis mediated by the intrinsic pathway, BAX/BAK triggers mitochondrial permeabilization and the release of cytochrome-c, followed by a dramatic remodelling of the mitochondrial network that results in mitochondrial herniation and the subsequent release of pro-inflammatory mitochondrial components. Here, we show that mitochondrial herniation and subsequent exposure of the inner mitochondrial membrane (IMM) to the cytoplasm, initiates a unique form of mitophagy to deliver these damaged organelles to lysosomes. IMM-induced mitophagy occurs independently of canonical PINK1/Parkin signalling and is driven by ubiquitination of the IMM. Our data suggest IMM-induced mitophagy is an additional safety mechanism that cells can deploy to contain damaged mitochondria. It may have particular relevance in situations where caspase activation is incomplete or inhibited, and in contexts where PINK1/Parkin-mitophagy is impaired or overwhelmed.
(© 2024. The Author(s).)
Databáze: MEDLINE
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