Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy.
Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy.
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DOI：
10.1038/s41467-017-00520-9
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发表时间：
2017-09-15
影响因子：
16.6
通讯作者：
Yan Z
中科院分区：
文献类型：
--
作者：
Laker RC;Drake JC;Wilson RJ;Lira VA;Lewellen BM;Ryall KA;Fisher CC;Zhang M;Saucerman JJ;Goodyear LJ;Kundu M;Yan Z
线粒体健康对于骨骼肌功能至关重要，通过线粒体生物发生和通过线粒体自噬去除受损/功能失调的线粒体进行运动训练可以改善线粒体健康。运动诱发线粒体自噬的机制尚未完全阐明。在这里，我们发现小鼠急性跑步机跑步会导致骨骼肌运动后 3-12 小时的线粒体氧化应激和 6 小时的线粒体自噬。使用新型荧光报告基因 pMitoTimer 监测这些变化，该基因可以评估体内线粒体氧化应激和线粒体自噬，并且在此之前，酪氨酸 172 处的 AMP 激活蛋白激酶 (Ampk) 和丝氨酸 555 处的 unc-51（如自噬激活激酶 1 (Ulk1)）的磷酸化增加。使用在骨骼肌中表达显性失活和组成性活性 Ampk 的小鼠，我们证明了Ulk1 的激活依赖于 Ampk。此外，运动引起的代谢适应需要 Ulk1。这些发现提供了运动诱导线粒体自噬的直接证据，并证明了 Ampk-Ulk1 信号在骨骼肌中的重要性。运动与生物发生和功能障碍线粒体的去除有关。在这里，作者使用线粒体报告基因来证明小鼠运动后线粒体自噬的发生，并表明这依赖于 AMPK 和 ULK1 信号传导。
Mitochondrial health is critical for skeletal muscle function and is improved by exercise training through both mitochondrial biogenesis and removal of damaged/dysfunctional mitochondria via mitophagy. The mechanisms underlying exercise-induced mitophagy have not been fully elucidated. Here, we show that acute treadmill running in mice causes mitochondrial oxidative stress at 3–12 h and mitophagy at 6 h post-exercise in skeletal muscle. These changes were monitored using a novel fluorescent reporter gene, pMitoTimer, that allows assessment of mitochondrial oxidative stress and mitophagy in vivo, and were preceded by increased phosphorylation of AMP activated protein kinase (Ampk) at tyrosine 172 and of unc-51 like autophagy activating kinase 1 (Ulk1) at serine 555. Using mice expressing dominant negative and constitutively active Ampk in skeletal muscle, we demonstrate that Ulk1 activation is dependent on Ampk. Furthermore, exercise-induced metabolic adaptation requires Ulk1. These findings provide direct evidence of exercise-induced mitophagy and demonstrate the importance of Ampk-Ulk1 signaling in skeletal muscle. Exercise is associated with biogenesis and removal of dysfunctional mitochondria. Here the authors use a mitochondrial reporter gene to demonstrate the occurrence of mitophagy following exercise in mice, and show this is dependent on AMPK and ULK1 signaling.
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DOI：
10.1083/jcb.201008084
发表时间：
2010-11-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jin SM;Lazarou M;Wang C;Kane LA;Narendra DP;Youle RJ
通讯作者：
Youle RJ
影响因子：
6.1
作者：
Chen S;Zhu P;Guo HM;Solis RS;Wang Y;Ma Y;Wang J;Gao J;Chen JM;Ge Y;Zhuang J;Li J
通讯作者：
Li J
AMP激活的蛋白激酶对ULK1（HATG1）的磷酸化将能量传感连接到线粒体。
DOI：
10.1126/science.1196371
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Egan DF;Shackelford DB;Mihaylova MM;Gelino S;Kohnz RA;Mair W;Vasquez DS;Joshi A;Gwinn DM;Taylor R;Asara JM;Fitzpatrick J;Dillin A;Viollet B;Kundu M;Hansen M;Shaw RJ
通讯作者：
Shaw RJ
影响因子：
4.8
作者：
Fujii, N;Hirshman, MF;Goodyear, LJ
通讯作者：
Goodyear, LJ
影响因子：
4.1
作者：
BOVERIS, A;CHANCE, B
通讯作者：
CHANCE, B