Mitochondrial origins of the pressure to sleep
Dr. Raffaele Sarnataro
Fulford Junior Research Fellow at Somerville College and Postdoctoral Fellow at the University of Oxford in the Miesenböck group. His research focuses on the bioenergetic molecular machinery and network dynamics of sleep-control neurons underlying the regulation of sleep. He holds a DPhil in Neuroscience from the University of Oxford and degrees in Molecular and Cell Biology from the Scuola Normale Superiore and the University of Pisa.
In this study, researchers explored why animals feel increasing sleep pressure by focusing on a small group of sleep‑regulating neurons in fruit flies that innervate a part of the brain called the dorsal fan‑shaped body. They found that after keeping flies awake, these neurons—but not everywhere in the brain—begin to produce many more molecules involved in mitochondrial energy production, the tiny power factories inside cells.
At the same time, the mitochondria in these cells change shape: they fragment, recycle more through a process called mitophagy, and increase contact with other cell structures. These morphological changes reverse after the flies are allowed to sleep again.
The key mechanism appears to involve an imbalance: during wakefulness, these sleep-active neurons are less electrically active, so they do not use much ATP (the cell’s energy currency), but mitochondrial activity continues, leading to an overflow of electrons within the respiratory chain. That overflow causes electrons to leak out, producing reactive oxygen species and signalling a kind of metabolic stress.
Crucially, when the team engineered mitochondria to let excess electrons escape harmlessly, the drive to sleep lessened; when they forced additional electron supply without increasing energy use, sleep pressure rose. Altering mitochondrial morphology in these neurons had directly predictable effects on sleep: forcing mitochondria into elongated, fused forms increased neuronal excitability and spontaneous and rebound sleep, while fragmenting them reduced both.
The researchers propose that these neurons act like built‑in “circuit breakers” that monitor electron overload—when too many electrons accumulate relative to ATP demand, they trigger sleep to restore balance and protect cells from oxidative stress. This discovery suggests that comparable mitochondrial mechanisms regulate drives like sleep and hunger in mammals, hinting at a conserved evolutionary origin of how innate behaviours are controlled.
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Recent publications from ESRS members
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