AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1 (vol 22, pg 419, 2015)

被引：63

作者：

Strappazzon, F.

Nazio, F.

Corrado, M.

Cianfanelli, V.

Romagnoli, A.

Fimia, G. M.

Campello, S.

Nardacci, R.

Piacentini, M.

Campanella, M.

Cecconi, F.

机构：

[1] IRCCS Fondazione Santa Lucia, Rome

[2] Department of Biology, University of Rome Tor Vergata, Rome

[3] Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Padova

[4] Unit of Cell Stress and Survival, Danish Cancer Society Research Center, Copenhagen

[5] IRCCS Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, Rome

[6] Department of Biological and Environmental Sciences and Technolgies (DiSTeBA), University of Salento, Lecce

[7] Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London

[8] European Brain Research Institute (EBRI), Rita Levi-Montalcini Foundation, Rome

来源：

CELL DEATH AND DIFFERENTIATION | 2015年 / 22卷 / 03期

基金：

英国生物技术与生命科学研究理事会;

关键词：

D O I：

10.1038/cdd.2014.190

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：517 / 517

页数：1