Year: 2014
Type: article
Abstract: Damaged mitochondria are eliminated by mitophagy, a selective form of autophagy whose dysfunction associates with neurodegenerative diseases. PINK1, PARKIN and p62/SQTMS1 have been shown to regulate mitophagy, leaving hitherto ill-defined the contribution by key players in 'general' autophagy. In basal conditions, a pool of AMBRA1 - an upstream autophagy regulator and a PARKIN interactor - is present at the mitochondria, where its pro-autophagic activity is inhibited by Bcl-2. Here we show that, upon mitophagy induction, AMBRA1 binds the autophagosome adapter LC3 through a LIR (LC3 interacting region) motif, this interaction being crucial for regulating both canonical PARKIN-dependent and -independent mitochondrial clearance. Moreover, forcing AMBRA1 localization to the outer mitochondrial membrane unleashes a massive PARKIN- and p62-independent but LC3-dependent mitophagy. These results highlight a novel role for AMBRA1 as a powerful mitophagy regulator, through both canonical or noncanonical pathways.
Source: Cell Death and Differentiation
DOI: 10.1038/cdd.2014.139
Institutions: University of Rome Tor Vergata, Fondazione Santa Lucia, Veneto Institute of Molecular Medicine, Dulbecco Telethon Institute, Danish Cancer Society, Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani, University of Salento, University of London, Royal Veterinary College, European Brain Research Institute, University College London
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,790
OpenAlex ID: W1992947862