A potassium channel β-subunit couples mitochondrial electron transport to sleep

Kempf, Anissa and Song, Seoho M. and Talbot, Clifford B. and Miesenböck, Gero. (2019) A potassium channel β-subunit couples mitochondrial electron transport to sleep. Nature, 568 (7751). pp. 230-234.

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Official URL: https://edoc.unibas.ch/85417/

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The essential but enigmatic functions of sleep; 1,2; must be reflected in molecular changes sensed by the brain's sleep-control systems. In the fruitfly Drosophila, about two dozen sleep-inducing neurons; 3; with projections to the dorsal fan-shaped body (dFB) adjust their electrical output to sleep need; 4; , via the antagonistic regulation of two potassium conductances: the leak channel Sandman imposes silence during waking, whereas increased A-type currents through Shaker support tonic firing during sleep; 5; . Here we show that oxidative byproducts of mitochondrial electron transport; 6,7; regulate the activity of dFB neurons through a nicotinamide adenine dinucleotide phosphate (NADPH) cofactor bound to the oxidoreductase domain; 8,9; of Shaker's K; V; β subunit, Hyperkinetic; 10,11; . Sleep loss elevates mitochondrial reactive oxygen species in dFB neurons, which register this rise by converting Hyperkinetic to the NADP; +; -bound form. The oxidation of the cofactor slows the inactivation of the A-type current and boosts the frequency of action potentials, thereby promoting sleep. Energy metabolism, oxidative stress, and sleep-three processes implicated independently in lifespan, ageing, and degenerative disease; 6,12-14; -are thus mechanistically connected. K; V; β substrates; 8,15,16; or inhibitors that alter the ratio of bound NADPH to NADP; +; (and hence the record of sleep debt or waking time) represent prototypes of potential sleep-regulatory drugs.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Neurobiology (Kempf)
UniBasel Contributors:Kempf, Anissa
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 Feb 2022 13:28
Deposited On:24 Feb 2022 13:28

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