Mitochondria May Be the Brain’s Secret Sleep Switch

By World Mitochondria Society 

Why do we feel so tired when we don’t sleep?

A new study published in Nature suggests the answer may lie deep inside our brain cells, specifically in their mitochondria, the tiny energy-producing structures often called the cell’s “powerhouses.”
Researchers from the University of Oxford found that when fruit flies were sleep-deprived, a specific group of brain cells showed dramatic changes in their mitochondria. These neurons, which help control the urge to sleep, responded to sleep loss by ramping up energy production and reorganizing their internal machinery.

Mitochondria and Sleep Pressure

They discovered that sleep pressure, what makes us feel sleepy, builds up when mitochondria in key neurons become overworked. 
After rest, these changes reversed, suggesting that mitochondria help the brain recover. Even more striking, the scientists were able to dial sleepiness up or down by changing how the mitochondria worked.
When the mitochondria were forced to split into smaller fragments, the flies slept less. When mitochondria were fused into longer structures, the flies felt a stronger need to sleep.

This discovery adds a surprising new piece to the puzzle of sleep science. Until now, sleep was mostly studied as a brain-wide process involving electrical signals or chemical messengers. But this study shows that the buildup of sleep pressure might begin with stress inside individual brain cells.

What’s next?

This research could one day help scientists design treatments for sleep disorders by targeting mitochondrial health. It also opens the door to rethinking sleep not just as a brain state, but as a metabolic response to cellular energy needs.

A new study published in Nature by Gero Miesenböch : https://www.nature.com/articles/s41586-025-09261-y