Atg4D at the interface between autophagy and apoptosis

Research output: Contribution to journalArticle (Academic Journal)peer-review

42 Citations (Scopus)

Abstract

The Atg4 family of endopeptidases regulates autophagosome biogenesis by priming newly synthesised Atg8 to enable covalent attachment of phosphatidylethanolamine, and by delipidating Atg8 at the lysosomal fusion step. Control of Atg4 activity is therefore crucial, although little is known about how these molecules are regulated in living cells. We have found that one human Atg4 family member (Atg4D) is cleaved at DEVD63K by caspase-3 during apoptosis. Importantly, our studies suggest that native Atg4D is enzymatically inactive, but gains GABARAP-L1 priming/delipidation activity following caspase cleavage. Caspase-cleaved Atg4D is also highly cytotoxic; however, toxicity is not due to enhanced autophagy, but is mediated by a putative C-terminal BH3 domain, and is associated with transient recruitment of Atg4D to mitochondria.
Translated title of the contributionAtg4D at the interface between autophagy and apoptosis
Original languageEnglish
Pages (from-to)1057 - 1059
Number of pages3
JournalAutophagy
Volume5 (7)
DOIs
Publication statusPublished - Oct 2009

Bibliographical note

Other: First published online. Punctum to: Betin VMS, Lane JD. Caspase cleavage of the autophagin Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis. J Cell Sci 2009; 122:2554-66; PMID: 19549685; DOI: 10.1242/jcs.046250

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