Restricted mitochondrial protein acetylation initiates mitochondrial autophagy

被引：90

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

共 50 条

[1] The mitochondrial permeability transition initiates autophagy in rat hepatocytes
Elmore, SP
Qian, T
Grissom, SF
Lemasters, JJ
FASEB JOURNAL, 2001, 15 (10): : 2286 - +
[2] Mitochondrial protein acetylation regulates metabolism
Anderson, Kristin A.
Hirschey, Matthew D.
LYSINE-BASED POST-TRANSLATIONAL MODIFICATION OF PROTEINS, 2012, 52 : 23 - 35
[3] Calorie restriction alters mitochondrial protein acetylation
Schwer, Bjoern
Eckersdorff, Mark
Li, Yu
Silva, Jeffrey C.
Fermin, Damian
Kurtev, Martin V.
Giallourakis, Cosmas
Comb, Michael J.
Alt, Frederick W.
Lombard, David B.
AGING CELL, 2009, 8 (05): : 604 - 606
[4] The roles of a mitochondrial protein Miga in autophagy
Xu, Lingna
Wang, Liquan
Tong, Chao
AUTOPHAGY, 2023, 19 (07) : 2151 - 2152
[5] ROS-induced mitochondrial depolarization initiates PARK2/PARKIN-dependent mitochondrial degradation by autophagy
Wang, Yuqing
Nartiss, Yulia
Steipe, Boris
McQuibban, G. Angus
Kim, Peter K.
AUTOPHAGY, 2012, 8 (10) : 1462 - 1476
[6] The role of protein acetylation in regulating mitochondrial fusion and fission
Uddin, Golam M.
Abbas, Rafa
Shutt, Timothy E.
BIOCHEMICAL SOCIETY TRANSACTIONS, 2021, 49 (06) : 2807 - 2819
[7] Protein acetylation links the circadian clock to mitochondrial function
Rey, Guillaume
Reddy, Akhilesh B.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (09) : 3210 - 3211
[8] ACETYLATION OF MITOCHONDRIAL PROTEINS
Hirschey, Matthew D.
Shimazu, Tadahiro
Huang, Jing-Yi
Verdin, Eric
METHODS IN ENZYMOLOGY, VOL 457: MITOCHONDRIAL FUNCTION, PARTB MITOCHONDRIAL PROTEIN KINASES, PROTEIN PHOSPHATASES AND MITOCHONDRIAL DISEASES, 2009, 457 : 137 - 147
[9] RETRACTED: Mitochondrial Protein Acetylation Mediates Nutrient Sensing of Mitochondrial Protein Synthesis and Mitonuclear Protein Balance (Retracted Article)
Di Domenico, Antonella
Hofer, Annette
Tundo, Federica
Wenz, Tina
IUBMB LIFE, 2014, 66 (11) : 793 - 802
[10] Chronic Ethanol Consumption Induces Mitochondrial Protein Acetylation in the Kidney
Harris, Peter S.
Roy, Samantha R.
Coughlan, Christina M.
Roede, James R.
Shearn, Colin T.
Fritz, Kristofer S.
FREE RADICAL BIOLOGY AND MEDICINE, 2014, 76 : S104 - S104

← 1 2 3 4 5 →