Restricted mitochondrial protein acetylation initiates mitochondrial autophagy

被引：93

作者：

Webster, Bradley R. ^{[1
]}

Scott, Iain ^{[1
]}

Han, Kim ^{[1
]}

Li, Jian H. ^{[1
]}

Lu, Zhongping ^{[1
]}

Stevens, Mark V. ^{[1
]}

Malide, Daniela ^{[2
]}

Chen, Yong ^{[3
]}

Samsel, Leigh ^{[4
]}

Connelly, Patricia S. ^{[5
]}

Daniels, Mathew P. ^{[5
]}

Mccoy, J. Philip, Jr. ^{[4
]}

Combs, Christian A. ^{[2
]}

Gucek, Marjan ^{[3
]}

Sack, Michael N. ^{[1
]}

机构：

[1] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA

[2] NHLBI, Light Microscopy Core, NIH, Bethesda, MD 20892 USA

[3] NHLBI, Prote Core, NIH, Bethesda, MD 20892 USA

[4] NHLBI, Flow Cytometry Core, NIH, Bethesda, MD 20892 USA

[5] NHLBI, Electron Microscopy Core, NIH, Bethesda, MD 20892 USA

来源：

JOURNAL OF CELL SCIENCE | 2013年 / 126卷 / 21期

关键词：

GCN5L1; SIRT3; Mitochondrial autophagy; Acetylation; Parkin; SIRT3; DEACETYLASE; IDENTIFICATION; SPERMIDINE; MECHANISM; MUTATION; PROMOTES; PARKIN;

D O I：

10.1242/jcs.131300

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Because nutrient-sensing nuclear and cytosolic acetylation mediates cellular autophagy, we investigated whether mitochondrial acetylation modulates mitochondrial autophagy (mitophagy). Knockdown of GCN5L1, a component of the mitochondrial acetyltransferase machinery, diminished mitochondrial protein acetylation and augmented mitochondrial enrichment of autophagy mediators. This program was disrupted by SIRT3 knockdown. Chronic GCN5L1 depletion increased mitochondrial turnover and reduced mitochondrial protein content and/or mass. In parallel, mitochondria showed blunted respiration and enhanced 'stress-resilience'. Genetic disruption of autophagy mediators Atg5 and p62 (also known as SQSTM1), as well as GCN5L1 reconstitution, abolished deacetylation-induced mitochondrial autophagy. Interestingly, this program is independent of the mitophagy E3-ligase Parkin (also known as PARK2). Taken together, these data suggest that deacetylation of mitochondrial proteins initiates mitochondrial autophagy in a canonical autophagy-mediator-dependent program and shows that modulation of this regulatory program has ameliorative mitochondrial homeostatic effects.

引用

页码：4843 / 4849

页数：7