alt.hn

5/21/2025 at 4:03:36 PM

Mitochondria Are More Than Powerhouses–They're the Motherboard of the Cell

 https://www.scientificamerican.com/article/why-mitochondria-are-more-like-a-motherboard-than-the-powerhouse-of-the-cell/

by novia

5/21/2025 at 6:01:34 PM

I feel like the field of metabolic psychiatry is a very promising one. I can say from personal experience that switching to a ketogenic diet along with regular monitoring my blood ketone levels has had a huge impact on my ADHD related doldrums. Over the past two years it has helped me with the motivation and drive to lose weight, consistently exercise, and made it easier to create new habits which seem to have stuck. It seems strange that simply (although radically) altering your diet can lead to a life changing virtuous circle, but that's been my experience.

by spudlyo

5/21/2025 at 7:22:38 PM

For others: most people don't need to go full keto. Just reducing sugars in general helps a lot of people. Refined sugars especially.

I also have ADHD and caffeine/sugar make my symptoms way worse. If I abstain from caffeine the difference is huge.

Alcohol is also something that really screws with ADHD. One drink can have weeks of effects.

by chneu

5/21/2025 at 8:54:11 PM

I think you might want to look into supplementing vitamin B1. In my personal experience sugar is not in itself the problem, but an impaired ability to process, or utilize, sugar can be. Many caffeinated beverages contain B1-inactivating tannins (tea, coffee), and consuming caffeine on an empty stomach, when blood sugar is already low, can cause mild deprivation of nerve tissues leading to impaired functioning.

Alcohol famously disrupts the metabolism of B1, making it ineffective in the body. In the extreme case it causes the Wernicke-Korsakoff syndrome which is exactly related to B1 metabolism.

The "insulinergic" role of potassium and so on in fruit juices also does make them easier to process in this way than something like coca cola.

by aeblyve

5/23/2025 at 1:39:42 AM

thanks for the advice but I just don't drink alcohol or caffeine anymore. Why supplement when I can just not do the thing in the first place?

by chneu

5/21/2025 at 7:21:58 PM

Seems a bit circular, no? Going on a diet to get the motivation to go on a diet. I'd wager a large part of your behavioral change was that you had already changed your behavior to get to that point.

by skeaker

5/21/2025 at 7:43:25 PM

To be fair, I probably wouldn't have been able to do it all if I didn't start out by eliminating work-related stress, which gave me some bandwidth to attempt something difficult. That was the first step in the flywheel, followed by diet, sleep prioritization, exercise, social connections, and structure/routine.

by spudlyo

5/21/2025 at 9:40:04 PM

Ymmv but I think the key here is the "virtuous cycle" bit, not the diet. When you gain control over a facet of your life and establish healthy habits, its bound to A) lead to more healthy habuts and B) lead to better mental/psychological hygene which is directly correlated wigh reduced adhd symptoms.

by DontchaKnowit

5/21/2025 at 6:41:40 PM

I don't know if you've read Brain Energy by Chris Palmer MD, but you'd probably really like it as a scientific confirmation of what you have experienced.

I used to be ketogenic, but ultimately moved to consuming more simple sugar from fruit juice etc per Ray Peat.

by aeblyve

5/21/2025 at 7:31:39 PM

There's a very, very low chance that consuming fruit juice will improve health.

Consuming fruit, sure.

Juice goes (almost) straight to the bloodstream and messes up an entire range of things (digestion, liver, glycation stuff, etc).

by literalAardvark

5/21/2025 at 9:02:15 PM

This is a belief that I held for years, leading me to avoid all of that stuff, yet increasing juice intake has been very helpful for feeling good and functioning well.

by aeblyve

5/22/2025 at 6:51:44 AM

Then increase fruit instead and get the best of both worlds.

by literalAardvark

5/21/2025 at 7:24:56 PM

Note: Ray Peat is a crazy person who Twitter bro-science picked up, the kind of guys who were previously into keto and supplements that don't do anything.

They're similar in that they love saturated fat and red meat, and think vegetable oils are bad, but he also wants you to eat ice cream and sugar.

The ice cream part is possibly correct: https://www.theatlantic.com/magazine/archive/2023/05/ice-cre...

by astrange

5/21/2025 at 8:48:28 PM

More-or-less, I guess. The methods work well for my feeling good and functioning well. e.g., no more migraines, reduced intensity of springtime allergies, more energy, better resistance to stress, etc.

by aeblyve

5/21/2025 at 8:22:01 PM

"you'd probably really like it as a scientific confirmation of what you have experienced."

So, bias confirmation? That is the opposite of scientific.

by IAmBroom

5/21/2025 at 8:44:42 PM

I did use the bad word "confirmation", but I don't think it's harmful to look at scientific dialogue which aligns with what one experiences so as to understand that experience better, from new perspectives, find caveats, etc.

If we believe that our personal experiences can be an ingredient of real knowledge about the world, etc

by aeblyve

5/21/2025 at 7:33:26 PM

[dead]

by stefantalpalaru

5/21/2025 at 5:48:33 PM

Learning biology is a great insight to how humans think about complex systems. We tend to utilize a reductionist and engineering approach to figure out how things work. This is a perfectly valid approach when building up a complex system from knowable individual parts.

But when analyzing a complex biological system, we tend to make analogies to our own engineered components (motherboards, power sources, circuits). There are definitely a lot of similarities and it is a great way to understand one facet of the system. But it can also sometimes make us lose sight of the intertwining relationships among all of these parts through evolution.

The analogy of our genome to an informational blueprint is one of the best examples of the multi-faceted nature of biology. While the sequence of bases contained within DNA (primary structure) is informational, the complex structures the molecule itself (chromatin structure) also have mechanistic purposes.

We build engineered components to be controllable and independent so we can better assess how the system is working. However, that is not an explicit goal with biology. Biological "components" settle into the best form for the given environment over time even if it creates a potential "mess" of connections and relationships.

I think this is also why biology takes a long time to "sink in" while learning compared to other technical fields. It's very easy to over-train your mental biological model on one facet of the system and lose sight of the others.

It is not uncommon to see the same terminology used in very different ways in various sub-fields of biology. Gene Ontology is also a great example of this as people have found there are biases associated with what the originator lab is studying at the time. Genes with pleiotropic function will tend to get assigned function that's more relevant to what the lab is interested in.

Sometimes I wonder if we are really equipped to navigate it and understand it. Maybe AI/computation is really the only way to try to have a holistic view of the complexities. Perhaps trying to understand biology with our biological brain has inherent limitations like a piece of software trying to understand the hardware it resides in.

by daemonk

5/21/2025 at 7:35:01 PM

> Sometimes I wonder if we are really equipped to navigate it and understand it. Maybe AI/computation is really the only way to try to have a holistic view of the complexities. Perhaps trying to understand biology with our biological brain has inherent limitations like a piece of software trying to understand the hardware it resides in.

This is a fascinating thought.

by christopherscot

5/21/2025 at 5:41:42 PM

This metaphor may be misleading. For a compelling alternate view, read the excellent: "Is the cell really a machine?" https://www.sciencedirect.com/science/article/abs/pii/S00225...

From the article:

"It has become customary to conceptualize the living cell as an intricate piece of machinery, different to a man-made machine only in terms of its superior complexity ......"

" ..... However, the recent introduction of novel experimental techniques capable of tracking individual molecules within cells in real time is leading to the rapid accumulation of data that are inconsistent with an engineering view of the cell ...... which emphasizes the dynamic, self-organizing nature of its constitution, the fluidity and plasticity of its components, and the stochasticity and non-linearity of its underlying processes."

by neosat

5/22/2025 at 8:06:18 PM

At the scale of a cell, magnetic field becomes like water - a real tangible thing that dominates physics. We have a bunch of formulas that explain the magnetic field, but we lack intuitive understanding that's gained with practice. This is what I think makes a cell so incomprehensible to us: things we can create are so large that the magnetic field is negligible, and our engineered systems behave like a bunch of gears.

by akomtu

5/21/2025 at 5:22:40 PM

If you like Mitochondria stuff, This book about the Krebs cycle and how it was discovered is pretty good: https://nick-lane.net/books/transformer-the-deep-chemistry-o...

The short answer is: First you have to murder a pigeon to extract fresh breast muscle cells. Then you put those cells in a manometer which uses columns of water to measure respiration via tiny changes in gas volume. From there you can add various things like citric acid and see how that affects respiration.

So figuring out mitochondria required murdering a large number of pigeons. Their breast muscles have some of the highest rates of respiration known, many times better then ours.

Reading this book inspired me to attempt to improve my mitochondrial health. So far the only stuff that seems to make a difference is NAD+ and Creatine.

by opwieurposiu

5/21/2025 at 7:03:07 PM

> First you have to murder a pigeon to extract fresh breast muscle cells.

Tom Lehrer would approve!

"We'll murder them all amid laughter and merriment, except for the few we take home to experiment."

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

by DonHopkins

5/21/2025 at 7:45:40 PM

You’ve cursed me to play the countries of the world song in my head all day, again.

by kridsdale1

5/21/2025 at 5:36:07 PM

How did you measure your mitochondrial health, short of extracting fresh breast muscle cells and putting them in a manometer?

by analog31

5/21/2025 at 7:27:02 PM

Personally I inherited a mitochondria disease (LHON), so I'll be able to tell if mine becomes bad because I'll go blind.

Can't recommend you do this though.

by astrange

5/22/2025 at 2:47:29 PM

I do group fitness classes, like CrossFit, body combat, spin class. When you have a room full of people all doing the same thing you can quickly tell which things you are above or below average at. Not very scientific perhaps but this is my current strategy.

For me I am below average at endurance, so that is where I assume the mitochondria come in.

by opwieurposiu

5/21/2025 at 5:38:03 PM

That's the clever bit - you extract them from pigeons instead!

by exe34

5/21/2025 at 7:44:42 PM

+1

Also supplementing with NAD+ and creatine for this reason. I also do PQQ and CoQ10 to de-bottleneck other phases of the Krebs.

by kridsdale1

5/21/2025 at 10:28:13 PM

The story of mitochondria is one of input mismatches. You get no UV, yet are warm. You see blue light, yet it’s night time. It’s day time, yet there is no NIR. You eat CHO heavy meals in the winter, yet nothing would grow at that latitude with the limited UV yield.

I could go into everything that goes into redox status, non-visual opsins, leptin and melanin, pgc1a, DHA, lack of cofactors (esp minerals), deuterium, and the list goes on… but nothing matters. All you need is to respect nature, wear blue light blockers at night, go outside, expose yourself to the elements, move, eat what you would have access to given the current UV yield, and supplement with tryspike.store’s MB-0.1 (due to soil depletion).

by peakskill

5/21/2025 at 7:28:36 PM

Eukaryogenesis is a fascinating topic, and "motherboard" doesn't do it justice.

For efficient respiration, you need to have the translation/transcription of certain ATP synthase genes near to the membrane for basically JIT-ing them when ready to maintain membrane potential, and hence energy generation. Otherwise, the membrane potential falls apart. This simple need is why there are zero multicellular bacteria and multicellularity evolved 6 times in eukaryotes.

By decoupling the rest of the genome from the JIT bits (ie, mitochondrial DNA), you can scale energy independently of genetic information. So if you need 1000x the energy, you need like 5% more DNA (mitochondrial DNA) instead of 1000x more DNA in your genome.

Some estimates say that our eukaryotic genes are in charge of 5000x more energy than the equivalent bacterial gene. Hence, our genomes can inflate that much and its fine. And they have. All that inflation lets us have bullshit hang around in our genome, and hey, sometimes evolution figures out something to do with all that bullshit. We evolved 1000x more complexity than bacteria because we decoupled the performance code from the rest of the code.

by koeng

5/21/2025 at 10:17:25 PM

This is a super interesting set of thoughts. Do you have any further reading that helped form this conclusion or is your intuition just that cool.

by ag_rin

5/21/2025 at 7:42:00 PM

I learned some new concepts from this post. You are hereby granted one hyper-upvote.

by kridsdale1

5/21/2025 at 9:17:15 PM

This article reminds me of something my psychiatrist said: "cells are typically classified by the role they perform, but I think it's better to classify them based on the type of mitochondria they have." Especially as it talked about the different mitochondria in neurons.

by smj-edison

5/21/2025 at 5:09:17 PM

There is all this variety in their behavior, shape, and influence on our biology, yet they have only 37 genes? How many nuclear genes augment these 37 to make all of this possible? Do any of these genes encode for the ribosome proteins necessary to convert the remaining genes into proteins?

What guides the behavior of a mitochondrion utterly lacking mtDNA? I suppose they still contain the proteins these genes code for, so maybe the genes are needed only for repair and reproduction.

by DFHippie

5/21/2025 at 6:45:06 PM

The genome of the rice plant is about 1.5x-2x the size of a human one.

by aeblyve

5/21/2025 at 10:22:07 PM

Fascinating article. Learned a lot. Especially about Lynn Margulis. What a great scientist. And she married Carl Sagan to boot.

Here's the part I don't understand about Mitochondria.

- I have a love-hate relationship with alcohol. I love it, it hates me. Turns out that alcohol really messes with mitochondria. And could be blamed for the inflammation and obesity epidemic (via mitochondrial disregulation).

- But then I see pics of people at beaches and public squares in the 60's and 70's. They were drinking way more than we do now. And they look skinny as heck. (As heck!)

- And apparently, for hundreds (thousands?) of years in various parts of the world (especially the middle ages West, and ancient Egypt), people pretty much drank water mixed with alcohol all day (it was safer than raw water), and their food was a type of thick beer porridge.

- So it can't be all that simple now, can it?

by profsummergig

5/21/2025 at 5:41:37 PM

“Endosymbiosis” always seemed so …eukaryocentric.

by whycome

5/21/2025 at 6:43:02 PM

Really enjoy this perspective. Mitochondria must be the true biological individuals, and the cells are just their "houses".

Otto Warburg wrote about the bioenergetics of cancer cells as favoring fermentation over respiration.

by aeblyve

5/21/2025 at 5:00:07 PM

There is a reason that longevists, longevity researchers, and biohackers focus on mitochondrial enhancement through various means, supplementing NAD/NR, Ubiquinol, PQQ, ALCAR, photobiomodulation, etc

"Your eyes transform light into electrical impulses that coalesce into an image in your visual field, and your ears transform air-pressure waves into electrical pulses that you eventually perceive as sounds. Likewise, mitochondria transform dozens of hormonal, metabolic, chemical, and other information streams into their electrical membrane potential. This “bioenergetic” state then leads to the production of secondary messenger molecules that are intelligible to the nucleus. So in the same way you read messages on your phone, which receives signals, transforms them and projects decipherable information onto its screen, the nucleus of your cells can “read” the environment through the MIPS that surrounds it. Rather than having supplementary roles like those of battery chargers, mitochondria are more like the motherboard of the cell. Genes sit inert in the nucleus until energy and the right message come along to turn some of them on and some others off. Mitochondria provide these messages, speaking the language of the epigenome—the malleable layer of regulation that sits on top of the genome to regulate its expression.

My colleague Timothy Shutt of the University of Calgary likes to call mitochondria the “CEO of the cell”: the chief executive organelle. This metaphor captures how mitochondria not only are involved in integrating information but also give orders. They dictate whether the cell divides, differentiates or dies. Indeed, mitochondria have a veto on cell life or death. If the MIPS deems it necessary, it triggers programmed cell death, or apoptosis—a form of self-sacrifice for the greater good of the organism.

So vital are mitochondria that in difficult times cells may donate entire mitochondria to other cells. “In cellular emergencies, newly arrived mitochondria might kick-start tissue repair, fire up the immune system or rescue distressed cells from death,” journalist Gemma Conroy noted in a Nature news story last April. Inside tumors, cancer cells and immune cells appear to compete for mitochondria, using them as a kind of bioweapon. An international effort I participated in, led by Jonathan R. Brestoff of the Washington University School of Medicine in St. Louis, recently created an entirely new lexicon to guide the emerging field of mitochondria transfer and transplantation. All well and good, you may think. What does all this mean for my health or how long I’m going to live?

The short answer is that it may have everything to do with human health. Diabetes, neurodegenerative conditions, cancer and even mental health illnesses are all emerging as metabolic disorders involving malfunctioning mitochondria. And these findings are indicating new routes for intervention.

Mitochondria drive health—or disease—in several ways. One route derives from their role as energy processors. In an electrical circuit, if we crank up the input voltage too much, we can blow it out. Similarly, if our cells are exposed to too much glucose or fat—or, worse, both together, causing what doctors refer to as glucolipotoxicity—the mitochondria undergo fission and fragment into little bits, accumulate mtDNA defects, and produce signals that end up prematurely aging or killing the cell. Experiments in cells and in mice have shown that pharmacologically or genetically preventing mitochondrial fission induced by excessive glucose and fats may protect against insulin resistance. Cancer, too, may be a disorder of cellular metabolism. Cancer cells can burn glucose without oxygen, which suggests either that something is wrong with their mitochondria or that they prefer to reserve mitochondria for use in cell division—and proliferation.

A second pathway is through mitochondria’s influence on gene expression. Mitochondrial signals alter the expression of more than 66 percent of genes in the nuclear chromosomes. By changing which genes are expressed and to what extent, mutations in mtDNA may completely alter the nature, behavior and stress resilience of cells and ultimately of the whole organism."

by matznerd

5/21/2025 at 7:17:33 PM

Metaphor taken way too far...

Who is the superIO chipset of the cell? Who are the VRMs?

by dmitrygr

5/21/2025 at 8:51:28 PM

SuperIO is the pores and ports system on the cellular membrane. Mitochondria are self-regulating (hence it's its own VRM), subject to added external control signals by hormonal receptors. And the nucleus is the tape drive.

by anticensor

5/21/2025 at 4:09:58 PM

In case of interest, maybe also see its related https://news.ycombinator.com/item?id=44052898

https://news.cnrs.fr/articles/a-map-of-energy-in-the-brain

Edit: I see that the other submission is marked as a "dupe": it is not - a shorter introduction to the article in Nature. The submission of this page is the narrative presentation from a main researcher.

Edit2: though of course if we wanted to consider a submission as "news" instead of "content", then the two submissions are related. Dang, maybe we could think of an HN feature where linked submissions are somehow grouped?

by mdp2021

5/21/2025 at 6:40:18 PM

Ray Peat PhD (RIP) and Chris Palmer MD have both emphasized the role of bioenergetics in human functioning, especially brain functioning.

by aeblyve