I also comment on our latest findings about mitochondria in fly sleep-control dFBNs, with my perspective on their neuroenergetic dynamics in light of the recent literature. 🪰
@medsci.ox.ac.uk @ox.ac.uk

I summarise cross-species experimental findings on how mitochondrial morphology, trafficking, and turnover relate to sleep and, more broadly, to behavioural homeostasis, and I examine the underlying neurobiology.

13/ 🧵 Finally, our findings conceptually align with known correlations between daily sleep and mass-specific oxygen consumption or brain mass (Fig from Savage et al 2007, each dot is a mammalian species), suggesting that sleep serves an ancient metabolic purpose also in mammals.

10/ Artificial induction of mitochondrial fission reduces baseline and rebound sleep as well as neuronal excitability, whereas promoting fusion produces the opposite effects.

9/ 🧵 If changes in mitochondrial morphofunction represent the homeostatic response to sleep loss, then experimentally inducing them in dFBNs is expected to shift the sleep set point.

7/ 🧵 The rearrangements in mitochondrial shape reflect a mismatch between ATP demand and electron flux causing the leak: during sleep deprivation, wake-promoting dopamine inhibits dFBNs, thus creating an electron surplus through elevated ATP concentrations.

6/ 🧵 This transcriptional reprogramming coincides with structural dynamics at the organelle level, such as mitochondrial fission, enhanced mitophagy, and more contacts between mitochondria and the endoplasmic reticulum.

5/ In these neurons, loss of sleep induces the selective upregulation of genes associated with the cells' aerobic energy metabolism, and a downregulation of genes encoding their presynaptic machinery.