RT Journal Article
SR Electronic
T1 Controlling the Mitochondrial Protonmotive Force with Light to Impact Cellular Stress Resistance
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 742536
DO 10.1101/742536
A1 Brandon J. Berry
A1 Adam J. Trewin
A1 Alexander S. Milliken
A1 Aksana Baldzizhar
A1 Andrea M. Amitrano
A1 Minsoo Kim
A1 Andrew P. Wojtovich
YR 2019
UL http://biorxiv.org/content/early/2019/08/21/742536.abstract
AB Mitochondrial respiration generates an electrochemical proton gradient across the mitochondrial inner membrane called the protonmotive force (PMF) to drive diverse functions and make ATP. Current techniques to manipulate the PMF are limited to its dissipation; there is no precise, reversible method to increase the PMF. To address this issue, we used an optogenetic approach and engineered a mitochondria-targeted light-activated proton pumping protein we called mitochondria-ON (mtON) to selectively increase the PMF. Here, mtON increased the PMF light dose-dependently, supported ATP synthesis, increased resistance to mitochondrial toxins, and modulated energy-sensing behavior in Caenorhabditis elegans. Moreover, transient mtON activation during hypoxia prevented the well-characterized adaptive response of hypoxic preconditioning. Our novel optogenetic approach demonstrated that a decreased PMF is both necessary and sufficient for hypoxia-stimulated stress resistance. Our results show that optogenetic manipulation of the PMF is a powerful tool to modulate metabolic and cell signaling outcomes.