Myristoylation confers noncanonical AMPK functions in autophagy selectivity and mitochondrial surveillance
Myristoylation confers noncanonical AMPK functions in autophagy selectivity and mitochondrial surveillance
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DOI：
10.1038/ncomms8926
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发表时间：
2015-08-01
影响因子：
16.6
通讯作者：
Mills, Gordon B.
中科院分区：
文献类型：
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作者：
Liang, Jiyong;Xu, Zhi-Xiang;Mills, Gordon B.
AMP激活的蛋白激酶（AMPK）在细胞能量感应和生物能量学中起着核心作用。然而，AMPK在监测线粒体损伤和诱导线粒体自噬中的作用仍不清楚。我们在此证明AMPK是有效的线粒体自噬所必需的。线粒体损伤诱导AMPK与ATG 16-ATG 5 -12的物理缔合以及VPS 34和ATG 16复合物与线粒体的AMPK依赖性募集。将AMPK靶向线粒体足以诱导线粒体自噬并促进细胞存活。AMPK向线粒体的募集需要AMPK β通过I型N-肉豆蔻酰转移酶1（NMT 1）的N-肉豆蔻酰化。我们的数据支持一个时空模型，其中AMPK与VPS 34和ATG 16复合物的组分结合到受损线粒体的募集调节选择性线粒体自噬以维持癌细胞活力。
AMP-activated protein kinase (AMPK) plays a central role in cellular energy sensing and bioenergetics. However, the role of AMPK in surveillance of mitochondrial damage and induction of mitophagy remains unclear. We demonstrate herein that AMPK is required for efficient mitophagy. Mitochondrial damage induces a physical association of AMPK with ATG16-ATG5-12 and an AMPK-dependent recruitment of the VPS34 and ATG16 complexes with the mitochondria. Targeting AMPK to the mitochondria is both sufficient to induce mitophagy and to promote cell survival. Recruitment of AMPK to the mitochondria requires N-myristoylation of AMPK beta by the type-I N-myristoyltransferase 1 (NMT1). Our data support a spatiotemporal model wherein recruitment of AMPK in association with components of the VPS34 and ATG16 complex to damaged mitochondria regulates selective mitophagy to maintain cancer cell viability.