Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins.
Proc Natl Acad Sci U S A
; 114(26): E5167-E5176, 2017 06 27.
Article
en En
| MEDLINE
| ID: mdl-28611221
ABSTRACT
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 mitochondria-targeted opsins were used to control complex physiological processes such as spontaneous beats in cardiac myocytes and glucose-dependent ATP increase in pancreatic ß-cells. Furthermore, our optometabolic tools allow modulation of mitochondrial functions in single cells and defined cell regions.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Señalización del Calcio
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Miocitos Cardíacos
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Células Secretoras de Insulina
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Potencial de la Membrana Mitocondrial
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Optogenética
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Channelrhodopsins
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Mitocondrias Cardíacas
Límite:
Animals
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Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2017
Tipo del documento:
Article
País de afiliación:
Israel