Exposure of the inner mitochondrial membrane triggers apoptotic mitophagy

Saunders, TL; Windley, SP; Gervinskas, G; Balka, KR; Rowe, C; Lane, R; Tailler, M; Nguyen, TN; Ramm, G; Lazarou, M; De Nardo, D; Kile, BT; McArthur, K

Author(s): Saunders, TL; Windley, SP; Gervinskas, G; Balka, KR; Rowe, C; Lane, R; Tailler, M; Nguyen, TN; Ramm, G; Lazarou, M; De Nardo, D; Kile, BT; McArthur, K;
Details: Publication Year 2024-02-23,Volume 31,Issue #3,Page 335-347
Journal Title: Cell Death & Differentiation
Abstract: 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.
Publisher: NPG
Keywords: Humans; *Mitophagy; *Ubiquitin-Protein Ligases/metabolism; Ubiquitination; Mitochondrial Membranes/metabolism; Protein Kinases/metabolism
Research Division(s): Ubiquitin Signalling
PubMed ID: 38396150/
Publisher's Version: https://doi.org/10.1038/s41418-024-01260-2
Open Access at Publisher's Site: https://doi.org/10.1038/s41418-024-01260-2
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-02-29 09:16:16

Last Modified: 2024-03-18 02:09:48