A new study by Oxford University researchers, published in Nature, reveals that the pressure to sleep arises from a build-up of electrical stress in the tiny energy generators inside brain cells.
The discovery offers a physical explanation for the biological drive to sleep and could reshape how scientists think about sleep, ageing, and neurological disease.
A metabolic trigger hidden in brain cells
Led by Professor Gero Miesenböck from DPAG, and Dr Raffaele Sarnataro at Oxford’s Centre for Neural Circuits and Behaviour, the team found that sleep is triggered by the brain’s response to a subtle form of energy imbalance. The key lies in mitochondria - microscopic structures inside cells that use oxygen to convert food into energy.
When the mitochondria of certain sleep-regulating brain cells (studied in fruit flies) become overcharged, they start to leak electrons, producing potentially damaging byproducts known as reactive oxygen species. This leak appears to act as a warning signal that pushes the brain into sleep, restoring equilibrium before damage spreads more widely.
‘You don’t want your mitochondria to leak too many electrons,’ said Dr Sarnataro. ‘When they do, they generate reactive molecules that damage cells.’
Sleep: a circuit-breaker against overload
The researchers found that specialised neurons act like circuit breakers—measuring this mitochondrial electron leak and triggering sleep when a threshold is crossed. By manipulating the energy handling in these cells—either increasing or decreasing electron flow—the scientists could directly control how much the flies slept.
Even replacing electrons with energy from light (using proteins borrowed from microorganisms) had the same effect: more energy, more leak, more sleep.
Professor Miesenböck said: ‘We set out to understand what sleep is for—and why we feel the need to sleep at all. Despite decades of research, no one had identified a clear physical trigger. Our findings show that the answer may lie in the very process that fuels our bodies: aerobic metabolism. In certain sleep-regulating neurons, we discovered that mitochondria—the cell’s energy producers—leak electrons when there is an oversupply. When the leak becomes too large, these cells act like circuit breakers, tripping the system into sleep to prevent overload.’
Broader implications for health and longevity
The findings help explain well-known links between metabolism, sleep, and lifespan. Smaller animals, which consume more oxygen per gram of body weight, tend to sleep more and live shorter lives. Humans with mitochondrial diseases often experience debilitating fatigue even without exertion—now potentially explained by the same mechanism.
‘This research answers one of biology’s big mysteries,’ said Dr Sarnataro. ‘Why do we need sleep? The answer appears to be written into the very way our cells convert oxygen into energy.’
The authors of the research paper are Raffaele Sarnataro, Cecilia D. Velasco, Nicholas Monaco, Anissa Kempf and Gero Miesenböck
This research was funded by Wellcome and the European Research Council
Read the paper Mitochondrial origins of the pressure to sleep in full here