Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy
Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy
复制标题
AMPK 对 ULK1 的磷酸化调节 ULK1 易位至线粒体和线粒体自噬
DOI：
10.1016/j.febslet.2015.05.020
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发表时间：
2015-07-08
期刊：
影响因子：
3.5
通讯作者：
Feng, Du
中科院分区：
文献类型：
--
作者：
Tian, Weili;Li, Wen;Feng, Du
ULK-51样激酶（ULK 1）转位到功能障碍的线粒体并参与线粒体自噬，但负责ULK 1激活和转位的机制仍不清楚。在此，我们发现缺氧通过腺苷5 '-单磷酸（AMP）激活的蛋白激酶（AMPK）诱导ULK 1在丝氨酸-555处磷酸化。与野生型ULK 1不同，ULK 1（S555 A）突变体不能响应hypwda而易位到线粒体。AMPK的抑制或敲低阻止ULK 1易位并抑制线粒体自噬。最后，磷酸化模拟ULK 1（S555 D）突变体，而不是ULK 1（S555 A），拯救AMPK敲低细胞中的线粒体自噬。因此，我们得出结论，AMPK依赖的ULK 1磷酸化是至关重要的ULK 1的易位到线粒体和线粒体自噬反应缺氧应激。(C)2015年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
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.