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.

Autore Pugliese

• Fimia Gian Maria

Tutti gli autori

• Strappazzon F. , Nazio F. , Corrado M. , Cianfanelli V. , Romagnoli A. , Fimia G .M. , Campello S. , Nardacci R. , Piacentini M. , Campanella M. , Cecconi F.

Titolo volume/Rivista

CELL DEATH AND DIFFERENTIATION

Anno di pubblicazione

2015

ISSN

1476-5403

ISBN

Non Disponibile

Numero di citazioni Wos

50

Ultimo Aggiornamento Citazioni

25/04/2018

Numero di citazioni Scopus

58

Ultimo Aggiornamento Citazioni

26/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile