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Tkatch, T.* ; Greotti, E.* ; Baranauskas, G.* ; Pendin, D.* ; Roy, S.* ; Nita, L.I.* ; Wettmarshausen, J. ; Prigge, M.* ; Yizhar, O.* ; Shirihai, O.S.* ; Fishman, D.* ; Hershfinkel, M.* ; Fleidervish, I.A.* ; Perocchi, F. ; Pozzan, T.* ; Sekler, I.*

Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins.

Proc. Natl. Acad. Sci. U.S.A. 114, E5167-E5176 (2017)
Publ. Version/Full Text Research data DOI PMC
Key mitochondrial functions such as ATP production, Ca2+ uptake and release, and substrate accumulation depend on the proton electrochemical gradient (ΔμH+) across the inner membrane. Although several drugs can modulate ΔμH+, their effects are hardly reversible, and lack cellular specificity and spatial resolution. Although channelrhodopsins are widely used to modulate the plasma membrane potential of excitable cells, mitochondria have thus far eluded optogenetic control. Here we describe a toolkit of optometabolic constructs based on selective targeting of channelrhodopsins with distinct functional properties to the inner mitochondrial membrane of intact cells. We show that our strategy enables a light-dependent control of the mitochondrial membrane potential (Δψm) and coupled mitochondrial functions such as ATP synthesis by oxidative phosphorylation, Ca2+ dynamics, and respiratory metabolism. By directly modulating Δψm, the mitochondriatargeted opsinswere used to control complex physiological processes such as spontaneous beats in cardiac myocytes and glucose-dependent ATP increase in pancreatic β-cells. Furthermore, our optometabolic tools allow modulation of mitochondrial functions in single cells and defined cell regions.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Ca Signaling 2+ ; Mitochondria ; Mitochondrial Membrane Potential ; Optogenetic; Permeability Transition Pore; Endoplasmic-reticulum; Cell-differentiation; Calcium Uniporter; Optical Control; Indicators; Channels; Death; Channelrhodopsin-2; Determinants
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 114, Issue: 26, Pages: E5167-E5176 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Publishing Place Washington
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)