Sleep all comes down to the mitochondria (science.org)

So the ancient mystery of why we need sleep might have just been answered.

The paper shows that cell‑autonomous mild uncoupling in Drosophila sleep‑inducing neurons -- via Ucp4A/Ucp4C -- keeps the flies awake by lowering mitochondrial Δp and therefore electron leak. This suggests a biochemical rationale for sleep -- which is postponed by the uncoupler. That form of pharmacological manipulation is also a very local intervention and likely has never been tried in mammals. (Most mitochondrial uncouplers aren't that specific and don't cross the BBB very well. Even "safe" new ones like BAM15.) If the paper is correct, not only is the mystery solved, but "healthy" wakefulness-promoting drugs might be on the horizon.

I'm curious about what this means for deep vs. light sleepers, and for people who need more or less sleep than others. Perhaps those traits are modifiable.

Crazy. If true this solves the question why humans need sleep and could be a great direction to resolve further question about sleep diseases.

Something I thought was just an internet tale: mitochondria are close descendants of bacteria, and so taking antibiotics will potentially harm them. But turns out this is actually rooted in science ...

Happy to read that they didn't go for 'Mitochondria Are All You Need', such titles are making me tired

i wonder if it relates to that chronic laziness disease, i cant remember what its called

Given its role in energy transfer, does this suggest creatine might be a good supplement for improving sleep?

mitochondria are just so incredibly fascinating in every aspect

they are like another lifeform not just living in our lifeform but making it possible

even their mere existence might be alien or even explain the lack of alien life detected so far

PBS Space Time has yet another awesome episode on that

https://www.pbs.org/video/is-there-a-simple-solution-to-the-...

https://www.youtube.com/watch?v=abvzkSJEhKk

How far away are we from making this a pill? So we can stay up 18 hours a day, or something. Any estimates.

Any idea what foods or current methods, to trigger the same mechanism?

Electrons are all you need

"electrons flow through the respiratory chains of the respective feedback controllers like sand in the hourglass that determines when balance must be restored"

Wow, that is my new favorite sentence from any paper ever, replacing Mark Thomas' equally epic: "What it begins to suggest is that we’re looking at a Lord of the Rings-type world" from the legendary meeting at the Royal Society in London 2012/13.

https://www.nature.com/articles/nature.2013.14196

I wonder how this relates to sleep apnea, as in that state you sleep more the less oxygen you get. By the way, many people who don't think they have it yet feel tired during the day or simply feel like they need more sleep should get tested for it, as it's not just a problem for the obese.

Sleep is super important. I’ve seen too many workaholic types that barely sleep. So many of these folks end up with serious issues later in life.

The paper is here:

https://www.nature.com/articles/s41586-025-09261-y

Not an expert in this area, but the essay feels a bit like an oversimplification. Not only is this in flies, but I wasn't entirely convinced this isn't about rest rather than sleep per se. It's a cool paper, interesting to read and read about, but my hunch is there's more steps in the chain, and am not sure it will replicate in humans or even mammals. But maybe I'll be wrong.

Could this be an explanation for why people who go without sleep for long enough eventually just die? The Guinness Book of World Records doesn't accept records on staying awake for the same reason they don't accept records for the longest game of Russian Roulette.

So lack of sleep damages thr little critters.

When he says lack of "restorative" sleep, he means stage III NREM? I wish he were more precise.

The heart beats non-stop and doesn't sleep. How does this fit with this theory?

This has been known for a long time to those interested in the field.

Isn't mitochondria the hot new topic du jour (last couple of years) for bio? Is this kind of peak hype cycle?

Science follows the exact same cycle as tech ... I feel like the microbiome was huge and going to solve all our problems 8 years ago.

I don't want to sound jaded but history repeats itself in echoes - and these cycles seem somewhat predictable if the specific technology isn't predictable.

There is a difference between being physically tired as a result of metabolic effort, and being mentally tired/sleepy. Even if you lie on the couch all day you will still be tired come night time, and can not survive for long if deprived of sleep.

It seems the mental need for sleep comes from the brain needing offline (no sensory input) downtime for "housekeeping" activities - perhaps essentially organizing and filing away the day's short-term memories.

Increasing the count and efficiency of mitochondria is gonna be a big deal. ME/CFS is caused by these organelles not working as they should.

> If you need oxygen, then you need sleep!

Would this also correlate with the desire to yawn? I always heard that yawning was a response to needing more oxygen.

Funded primarily by UK and European taxpayers and foundations via 8 grants, predominantly from the Wellcome Trust, with additional support from EU research council and Swiss science programs.

I’m drawing a connection here between red light therapy being most beneficial if done in the morning.

Might mitochondria only be able to benefit from “recharging” in a recharge state?

Biochemists?

I wonder is this why creatine gives me more energy?