Exposure of the inner mitochondrial membrane triggers apoptotic mitophagy

Tahnee L. Saunders, Simon P. Windley, Gediminas Gervinskas, Katherine R. Balka, Caitlin Rowe, Rachael Lane, Maximilien Tailler, Thanh Ngoc Nguyen, Georg Ramm, Michael Lazarou, Dominic De Nardo, Benjamin T. Kile, Kate McArthur

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)335-347
Number of pages13
JournalCell Death and Differentiation
Volume31
Issue number3
DOIs
Publication statusPublished - Mar 2024

Cite this