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

Anissa Kempf, Seoho M. Song, Clifford B. Talbot and Gero Miesenböck ()
Additional contact information
Anissa Kempf: University of Oxford
Seoho M. Song: University of Oxford
Clifford B. Talbot: University of Oxford
Gero Miesenböck: University of Oxford

Nature, 2019, vol. 568, issue 7751, 230-234

Abstract: Abstract The essential but enigmatic functions of sleep1,2 must be reflected in molecular changes sensed by the brain’s sleep-control systems. In the fruitfly Drosophila, about two dozen sleep-inducing neurons3 with projections to the dorsal fan-shaped body (dFB) adjust their electrical output to sleep need4, 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 sleep5. Here we show that oxidative byproducts of mitochondrial electron transport6,7 regulate the activity of dFB neurons through a nicotinamide adenine dinucleotide phosphate (NADPH) cofactor bound to the oxidoreductase domain8,9 of Shaker’s KVβ subunit, Hyperkinetic10,11. 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 disease6,12–14—are thus mechanistically connected. KVβ substrates8,15,16 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.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-019-1034-5 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:568:y:2019:i:7751:d:10.1038_s41586-019-1034-5

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-019-1034-5

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().