期刊
FASEB JOURNAL
卷 34, 期 12, 页码 16333-16347出版社
WILEY
DOI: 10.1096/fj.202001150RR
关键词
anoxia; metabolism; optogenetics; uncoupling
资金
- National Institutes of Health [R01 NS092558, R01 NS115906]
- American Heart Association Predoctoral Fellowship [18PRE33990054]
- NIH Office of Research Infrastructure Programs [P40 OD010440]
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.
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