JUL 23, 2025

Can Mitochondria Explain the Need for Sleep?

WRITTEN BY: Carmen Leitch

People need to sleep, and sleep deprivation can cause many changes in the brain. But we have a poor understanding of why sleep is so crucial. New research has examined a fruit fly model to assess how sleep deprivation affects brain cells. This work has indicated that sleep is essential for the health of mitochondria–critical, power-generating organelles that are found in almost all cells. The pressure for sleep manifests as increases in electrical stress in mitochondria, which can only be relieved by sleep. The findings, which have suggested that sleep is an "inescapable consequence" of our cells' metabolic processes, have been reported in Nature.

In this work, the researchers compared the brain cells of fruit flies that had been deprived of sleep to those from flies that had sleep normally. One caveat of this study is that it was performed din fruit flies, and scientists have shown that sleep is required by fruit flies. Some researchers have noted that we actually do not have definitive proof that all animals with a nervous system enter a state of sleep, though the authors of this study have suggested that the presence of a nervous system does lead to that requirement. Researchers have also found sleep to be a itghtly controlled process in everyvertebrate species that has been carefully examined.

This latest work noted that as anaerobic metabolism arose with the evolution of eukaryotic cells, it led to the development of power-hungry nervous systems. They add that small animals tend to sleep more and have shorter lifespans than larger animals, which may be because there is more oxygen supplied to their cells (per gram of body weight) than larger animals, and smaller creatures have a 'hotter' metabolism than larger ones. People with mitochondrial disorders also tend to sleep more. Sleep could have arisen during evolution due to metabolic demands; as energy imbalances arise in an organism, sleep restores the necessary balance.

In the sleep-deprived fruit flies, mitochondria in sleep-regulating neurons began to leak electrons, which can lead to the production of reactive oxygen species, and more cellular damage. That leakiness seems to function as a warning signal that triggers the brain to sleep. Once sleep occurs, the leaks stop.

"You don't want your mitochondria to leak too many electrons," said first study author Dr. Raffaele Sarnataro of the University of Oxford. "When they do, they generate reactive molecules that damage cells."

Some neurons can sense the electrons leaking from mitochondria, leading to sleep. When the researchers altered those cells to either raise or lower the flow of electrons, they could control how much flies were sleeping.

When they replaced the electrons with light energy, the same process occurred: more energy led to mitochondrial leakiness, and more sleep.

"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," said corresponding study author Professor Gero Miesenböck of the University of Oxford. 

"This research answers one of biology's big mysteries," said Sarnataro. "Why do we need sleep? The answer appears to be written into the very way our cells convert oxygen into energy."

Sources: University of Oxford, Nature