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 Repjournal_title
EMBO reportsauthors
Berry BJ,Trewin AJ,Milliken AS,Baldzizhar A,Amitrano AM,Lim Y,Kim M,Wojtovich APdoi
10.15252/embr.201949113subject
Has Abstractpub_date
2020-04-03 00:00:00pages
e49113issue
4eissn
1469-221Xissn
1469-3178journal_volume
21pub_type
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