Optogenetic control of mitochondrial protonmotive force to impact cellular stress resistance.

Abstract:

: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.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Berry BJ,Trewin AJ,Milliken AS,Baldzizhar A,Amitrano AM,Lim Y,Kim M,Wojtovich AP

doi

10.15252/embr.201949113

subject

Has Abstract

pub_date

2020-04-03 00:00:00

pages

e49113

issue

4

eissn

1469-221X

issn

1469-3178

journal_volume

21

pub_type

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