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Neuronal AMPK coordinates mitochondrial energy sensing and hypoxia resistance in C. elegans.


ABSTRACT: 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.

SUBMITTER: Berry BJ 

PROVIDER: S-EPMC7756364 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Neuronal AMPK coordinates mitochondrial energy sensing and hypoxia resistance in C. elegans.

Berry Brandon J BJ   Baldzizhar Aksana A   Nieves Tyrone O TO   Wojtovich Andrew P AP  

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20201015 12


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 spatiotempor  ...[more]

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