Optogenetic control of mitochondrial protonmotive force to impact cellular stress resistance
Optogenetic control of mitochondrial protonmotive force to impact cellular stress resistance
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DOI：
10.15252/embr.201949113
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发表时间：
2020-02-11
期刊：
影响因子：
7.7
通讯作者：
Wojtovich, Andrew P.
中科院分区：
文献类型：
--
作者：
Berry, Brandon J.;Trewin, Adam J.;Wojtovich, Andrew P.
线粒体呼吸产生一个跨线粒体内膜的电化学质子梯度，称为质子动力（PMF），以驱动多种功能并合成ATP。目前的技术来操纵保偏光纤仅限于其耗散，然而，没有精确和可逆的方法来增加保偏光纤。为了解决这个问题，我们的目标是使用光遗传学方法，并设计了一种靶向光激活质子泵，我们将其命名为mtON（mtON），以选择性地增加秀丽隐杆线虫中的PMF。在这里，我们表明，mtON光活化增加PMF的剂量依赖性的方式，支持ATP的合成，增加线粒体毒素的抵抗力，并调节能量感应行为。此外，短暂的mtON激活过程中缺氧预处理阻止了良好的适应性反应的耐缺氧。我们的研究结果表明，PMF的光遗传学操纵是调节代谢和细胞信号传导的有力工具。
Mitochondrial respiration generates an electrochemical proton gradient across the mitochondrial inner membrane called protonmotive force (PMF) to drive diverse functions and synthesize ATP. Current techniques to manipulate the PMF are limited to its dissipation; yet, there is no precise and reversible method to increase the PMF. To address this issue, we aimed to use an optogenetic approach and engineered a mitochondria-targeted light-activated proton pump that we name mitochondria-ON (mtON) to selectively increase the PMF in Caenorhabditis elegans. Here we show that mtON photoactivation increases the PMF in a dose-dependent manner, supports ATP synthesis, increases resistance to mitochondrial toxins, and modulates energy-sensing behavior. Moreover, transient mtON activation during hypoxic preconditioning prevents the well-characterized adaptive response of hypoxia resistance. Our results show that optogenetic manipulation of the PMF is a powerful tool to modulate metabolism and cell signaling.