Optogenetic control of mitochondrial protonmotive force to impact cellular stress resistance

Research output: Contribution to journalArticle

Authors

  • Brandon J. Berry
  • Adam J. Trewin
  • Alexander S. Milliken
  • Aksana Baldzizhar
  • Andrea M. Amitrano
  • Yunki Lim
  • Minsoo Kim
  • Andrew P. Wojtovich

External Institution(s)

  • University of Rochester

Details

Original languageEnglish (US)
Article numbere49113
JournalEMBO Reports
Volume21
Issue number4
StatusPublished - Apr 3 2020
Peer-reviewedYes

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.

    Research areas

  • anoxia, hypoxia, ischemia reperfusion, metabolism, uncoupling

Citation formats

APA

Berry, B. J., Trewin, A. J., Milliken, A. S., Baldzizhar, A., Amitrano, A. M., Lim, Y., ... Wojtovich, A. P. (2020). Optogenetic control of mitochondrial protonmotive force to impact cellular stress resistance. EMBO Reports, 21(4), [e49113]. https://doi.org/10.15252/embr.201949113

Harvard

Berry, BJ, Trewin, AJ, Milliken, AS, Baldzizhar, A, Amitrano, AM, Lim, Y, Kim, M & Wojtovich, AP 2020, 'Optogenetic control of mitochondrial protonmotive force to impact cellular stress resistance', EMBO Reports, vol. 21, no. 4, e49113. https://doi.org/10.15252/embr.201949113