Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy

被引：170

作者：

Tian, Weili ^{[1
]}

Li, Wen ^{[1
]}

Chen, Yinqin ^{[2
]}

Yan, Zeming ^{[3
]}

Huang, Xia ^{[4
]}

Zhuang, Haixia ^{[4
]}

Zhong, Wangtao ^{[1
]}

Chen, Yusen ^{[1
]}

Wu, Wenxian ^{[1
]}

Lin, Chunxia ^{[1
]}

Chen, Hao ^{[1
]}

Hou, Xiaoyan ^{[1
]}

Zhang, Liangqing ^{[4
]}

Sui, Senfang ^{[5
]}

Zhao, Bin ^{[1
]}

Hu, Zhe ^{[4
]}

Li, Longxuan ^{[6
]}

Feng, Du ^{[1
]}

机构：

[1] Guangdong Med Coll, Affiliated Hosp, Inst Neurol, Guangdong Key Lab Age Related Cardiac Cerebral Va, Zhanjiang 524001, Guangdong, Peoples R China

[2] Guangdong Med Coll, Dept Vasc Surg Thyroid & Mammary Gland Surg, Zhanjiang 524001, Guangdong, Peoples R China

[3] Guangdong Med Coll, Dept Intervent Radiol, Zhanjiang 524001, Guangdong, Peoples R China

[4] Guangdong Med Coll, Dept Anesthesiol, Zhanjiang 524001, Guangdong, Peoples R China

[5] Tsinghua Univ, Sch Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China

[6] Pudong New Area, Dept Neurol, Gongli Hosp, Shanghai 200135, Peoples R China

来源：

FEBS LETTERS | 2015年 / 589卷 / 15期

关键词：

Mitophagy; UNC-51 like kinase; Adenosine 5 '-monophosphate (AMP)-activated protein kinase; Hypoxia; Autophagy; Mitochondria; AUTOPHAGOSOME FORMATION; KINASE ULK1; PROTEIN; MTORC1; ENERGY; FUNDC1; NIX;

D O I：

10.1016/j.febslet.2015.05.020

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：

UNC-51 like kinase (ULK1) translocates to dysfunctional mitochondria and is involved in mitophagy, but the mechanisms responsible for ULK1 activation and translocation remain unclear. Here, we found that hypoxia induces phosphoryladon of ULK1 at Serine-555 by Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK). Unlike wild-type ULK1, an ULK1 (S555A) mutant cannot translocate to mitochondria in response to hypwda. Inhibition or knockdown of AMPK prevents ULK1 translocation and inhibits mitophagy. Finally, the phospho-mimic ULK1 (S555D) mutant, but not ULK1 (S555A), rescues mitophagy in AMPK-knockdown cells. Thus, we conclude that AMPK-dependent phosphorylation of ULK1 is critical for translocation of ULK1 to mitochondria and for mitophagy in response to hypoxic stress. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：1847 / 1854

页数：8

共 36 条

[1] Atg13 and FIP200 act independently of Ulk1 and Ulk2 in autophagy induction
Alers, Sebastian
Loeffler, Antje S.
Paasch, Florian
Dieterle, Alexandra M.
Keppeler, Hildegard
Lauber, Kirsten
Campbell, David G.
Fehrenbacher, Birgit
Schaller, Martin
Wesselborg, Sebastian
Stork, Bjoern
[J]. AUTOPHAGY, 2011, 7 (12) : 1424 - 1433
[2] Role of AMPK-mTOR-Ulk1/2 in the Regulation of Autophagy: Cross Talk, Shortcuts, and Feedbacks
Alers, Sebastian
Loeffler, Antje S.
Wesselborg, Sebastian
Stork, Bjoern
[J]. MOLECULAR AND CELLULAR BIOLOGY, 2012, 32 (01) : 2 - 11
[3] The serine/threonine kinase ULK1 is a target of multiple phosphorylation events
Bach, Markus
Larance, Mark
James, David E.
Ramm, Georg
[J]. BIOCHEMICAL JOURNAL, 2011, 440 : 283 - 291
[4] Ammonia-induced autophagy is independent of ULK1/ULK2 kinases
Cheong, Heesun
Lindsten, Tullia
Wu, Junmin
Lu, Chao
Thompson, Craig B.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (27) : 11121 - 11126
[5] The kinase triad, AMPK, mTORC1 and ULK1, maintains energy and nutrient homoeostasis
Dunlop, Elaine A.
Tee, Andrew R.
[J]. BIOCHEMICAL SOCIETY TRANSACTIONS, 2013, 41 : 939 - 943
[6] ULK1 inhibits mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding
Dunlop, Elaine A.
Hunt, David K.
Acosta-Jaquez, Hugo A.
Fingar, Diane C.
Tee, Andrew R.
[J]. AUTOPHAGY, 2011, 7 (07) : 737 - 747
[7] The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR
Egan, Daniel F.
Kim, Joungmok
Shaw, Reuben J.
Guan, Kun-Liang
[J]. AUTOPHAGY, 2011, 7 (06) : 645 - 646
[8] Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, Daniel F.
Shackelford, David B.
Mihaylova, Maria M.
Gelino, Sara
Kohnz, Rebecca A.
Mair, William
Vasquez, Debbie S.
Joshi, Aashish
Gwinn, Dana M.
Taylor, Rebecca
Asara, John M.
Fitzpatrick, James
Dillin, Andrew
Viollet, Benoit
Kundu, Mondira
Hansen, Malene
Shaw, Reuben J.
[J]. SCIENCE, 2011, 331 (6016) : 456 - 461
[9] Molecular signaling toward mitophagy and its physiological significance
Feng, Du
Liu, Lei
Zhu, Yushan
Chen, Quan
[J]. EXPERIMENTAL CELL RESEARCH, 2013, 319 (12) : 1697 - 1705
[10] Cellular Internalization of Exosomes Occurs Through Phagocytosis
Feng, Du
Zhao, Wen-Long
Ye, Yun-Ying
Bai, Xiao-Chen
Liu, Rui-Qin
Chang, Lei-Fu
Zhou, Qiang
Sui, Sen-Fang
[J]. TRAFFIC, 2010, 11 (05) : 675 - 687

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