AMPK-mediated activation of MCU stimulates mitochondrial Ca2+ entry to promote mitotic progression
AMPK-mediated activation of MCU stimulates mitochondrial Ca2+ entry to promote mitotic progression
复制标题
AMPK 介导的 MCU 激活刺激线粒体 Ca2 进入，促进有丝分裂进展
DOI：
10.1038/s41556-019-0296-3
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发表时间：
2019-04-01
影响因子：
21.3
通讯作者：
Pan, Xin
中科院分区：
文献类型：
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作者：
Zhao, Haixin;Li, Teng;Pan, Xin
细胞改变生物能量以响应各种生物过程的需求的能力对于正常生理至关重要。能量感知和生产与高能量需求的细胞过程（如细胞分裂）的协调知之甚少。在这里，我们表明，细胞周期依赖性线粒体Ca2+瞬态连接能量传感线粒体活性有丝分裂的进展。线粒体Ca 2+单向转运体（MCU）在有丝分裂期间介导快速的线粒体Ca 2+瞬变。通过MCU耗竭抑制线粒体Ca2+瞬变导致纺锤体检查点依赖性有丝分裂延迟。细胞ATP水平在早期有丝分裂期间下降，并且线粒体Ca2+瞬变促进线粒体呼吸以恢复能量稳态。这是通过有丝分裂特异性MCU磷酸化和能量传感器AMP激活蛋白激酶（AMPK）的线粒体易位激活实现的。我们的研究结果确立了AMPK和MCU依赖的线粒体Ca（2+）信号在有丝分裂中的关键作用，并揭示了线粒体代谢适应急性细胞能量应激的机制。
The capacity of cells to alter bioenergetics in response to the demands of various biological processes is essential for normal physiology. The coordination of energy sensing and production with highly energy-demanding cellular processes, such as cell division, is poorly understood. Here, we show that a cell cycle-dependent mitochondrial Ca2+ transient connects energy sensing to mitochondrial activity for mitotic progression. The mitochondrial Ca2+ uniporter (MCU) mediates a rapid mitochondrial Ca2+ transient during mitosis. Inhibition of mitochondrial Ca2+ transients via MCU depletion causes spindle checkpoint-dependent mitotic delay. Cellular ATP levels drop during early mitosis, and the mitochondrial Ca2+ transients boost mitochondrial respiration to restore energy homeostasis. This is achieved through mitosis-specific MCU phosphorylation and activation by the mitochondrial translocation of energy sensor AMP-activated protein kinase (AMPK). Our results establish a critical role for AMPK- and MCU-dependent mitochondrial Ca(2+ )signalling in mitosis and reveal a mechanism of mitochondrial metabolic adaptation to acute cellular energy stress.