Organisms adapt to their environment through coordinated changes in mitochondrial function and metabolism. The mitochondrial protonmotive force (PMF) is an electrochemical gradient that powers ATP synthesis and adjusts metabolism to energetic demands via cellular signaling. It is unknown how or where transient PMF changes are sensed and signaled due to the lack of precise spatiotemporal control in vivo. We addressed this by expressing a light‐activated proton pump in mitochondria to spatiotemporally “turn off” mitochondrial function through PMF dissipation in tissues with light. We applied our construct—mitochondria‐OFF (mtOFF)—to understand how metabolic status impacts hypoxia resistance, a response that relies on mitochondrial function. Activation of mtOFF induced starvation‐like behavior mediated by AMP‐activated protein kinase (AMPK). We found prophylactic mtOFF activation increased survival following hypoxia, and that protection relied on neuronal AMPK. Our study links spatiotemporal control of mitochondrial PMF to cellular metabolic changes that mediate behavior and stress resistance.

中文翻译：

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神经元 AMPK 协调线虫中的线粒体能量感应和耐缺氧性

生物体通过线粒体功能和新陈代谢的协调变化来适应环境。线粒体质子动力 (PMF) 是一种电化学梯度，可为 ATP 合成提供动力，并通过细胞信号传导调节新陈代谢以满足能量需求。由于体内缺乏精确的时空控制，尚不清楚瞬态 PMF 变化如何或在何处被感知和发出信号。我们通过在线粒体中表达一个光激活的质子泵来解决这个问题，通过光组织中的 PMF 耗散在时空上“关闭”线粒体功能。我们应用我们的构建体——线粒体-OFF (mtOFF)——来了解代谢状态如何影响耐缺氧性，这是一种依赖于线粒体功能的反应。mtOFF 的激活诱导由 AMP 活化蛋白激酶 (AMPK) 介导的饥饿样行为。我们发现预防性 mtOFF 激活增加了缺氧后的存活率，并且这种保护依赖于神经元 AMPK。我们的研究将线粒体 PMF 的时空控制与介导行为和抗压性的细胞代谢变化联系起来。