‘I’m not lazy, it’s cellular self-care’

The Sleep Switch

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“As far as I know, the only reason we need to sleep […] is that we get sleepy.”
After half a century studying slumber, Dr. William Dement’s wry observation still rings true: our best cue to sleep is simply feeling tired. But what flips that “sleep switch”? New research published by Sarnataro et al. (2025) points to an answer deep inside our neurons, within their mitochondria, the tiny powerhouses tracking metabolic fatigue.

Working with Drosophila (fruit flies), scientists have discovered how sleep-promoting neurons in the brain act as sensors of metabolic strain. When flies are kept awake, these neurons burn less energy, causing their energy (ATP) stores to overflow.

The energy surplus drives the neurons’ mitochondria into overdrive, meaning the cell’s power stations start producing excess energy and stress signals. Specialized proteins, called hyperkinetic, can sense this metabolic stress, resulting in the release of warning signals from the cell.

When the warning signal becomes strong enough, the brain increases its drive for sleep, giving itself time to rebalance energy levels and repair oxidative damage. Researchers found that altering genes that control how mitochondria divide and fuse changes how long and deeply the flies sleep, showing that the way cells manage their power supply plays a direct role in when, and how well, we rest.

Sarnataro et al. also highlight that “oxygen-powered life” comes with a cost. Animals with faster metabolisms tend to live shorter lives and spend more time asleep. In humans, sleep supports newer roles such as memory consolidation and brain maintenance, but comparisons across species suggest its original function was metabolic. Even small differences in mitochondrial DNA can influence this energy balance, helping explain why some individuals need more sleep than others. These insights also shed light on why many people with mitochondrial disease experience chronic fatigue.

Rather than a passive retreat, sleep appears to be an active recalibration, a nightly reset that balances energy supply and demand. So, the next time you feel sleepy, don’t feel lazy. Think of it as your batteries gently nudging you to take a breather.

Original Article: Sarnataro R, Velasco CD, Monaco N, Kempf A, Miesenböck G. Mitochondrial origins of the pressure to sleep. Nature. 2025;645:722-728. doi:10.1038/s41586-025-09261-y.