[HN Gopher] Mitochondria Are More Than Powerhouses-They're the M...
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       Mitochondria Are More Than Powerhouses-They're the Motherboard of
       the Cell
        
       Author : novia
       Score  : 92 points
       Date   : 2025-05-21 16:03 UTC (6 hours ago)
        
 (HTM) web link (www.scientificamerican.com)
 (TXT) w3m dump (www.scientificamerican.com)
        
       | mdp2021 wrote:
       | 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?
        
       | pvg wrote:
       | https://archive.is/OiSlu
        
       | blacksmith_tb wrote:
       | Also there's recent research on cells exchanging mitochondria[1]
       | which is pretty surprising.
       | 
       | 1: https://www.nature.com/articles/d41586-025-01064-5
        
       | matznerd wrote:
       | 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."
        
       | givinguflac wrote:
       | Fascinating.
       | 
       | This may be relevant- I was just reading another article about
       | migratory bird mitochondrial transition when migrating or not.
       | 
       | https://www.quantamagazine.org/turbocharged-mitochondria-pow...
        
         | ChrisArchitect wrote:
         | Some discussion on that one:
         | https://news.ycombinator.com/item?id=44051652
        
       | DFHippie wrote:
       | 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.
        
         | aeblyve wrote:
         | The genome of the rice plant is about 1.5x-2x the size of a
         | human one.
        
       | opwieurposiu wrote:
       | 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.
        
         | analog31 wrote:
         | How did you measure your mitochondrial health, short of
         | extracting fresh breast muscle cells and putting them in a
         | manometer?
        
           | exe34 wrote:
           | That's the clever bit - you extract them from pigeons
           | instead!
        
           | astrange wrote:
           | 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.
        
         | sergeym wrote:
         | have you tried zone-2 training?
         | https://www.youtube.com/watch?v=-6PDBVRkCKc
        
         | DonHopkins wrote:
         | > 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
        
           | kridsdale1 wrote:
           | You've cursed me to play the countries of the world song in
           | my head all day, again.
        
         | kridsdale1 wrote:
         | +1
         | 
         | Also supplementing with NAD+ and creatine for this reason. I
         | also do PQQ and CoQ10 to de-bottleneck other phases of the
         | Krebs.
        
       | whycome wrote:
       | "Endosymbiosis" always seemed so ...eukaryocentric.
        
         | aeblyve wrote:
         | 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.
        
       | neosat wrote:
       | 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."
        
       | daemonk wrote:
       | 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.
        
         | christopherscot wrote:
         | > 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.
        
       | spudlyo wrote:
       | 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.
        
         | aeblyve wrote:
         | 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.
        
           | astrange wrote:
           | 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...
        
             | aeblyve wrote:
             | 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.
        
           | literalAardvark wrote:
           | 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).
        
             | aeblyve wrote:
             | 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.
        
           | IAmBroom wrote:
           | "you'd probably really like it as a scientific confirmation
           | of what you have experienced."
           | 
           | So, bias confirmation? That is the opposite of scientific.
        
             | aeblyve wrote:
             | 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
        
         | skeaker wrote:
         | 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.
        
           | spudlyo wrote:
           | 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.
        
         | chneu wrote:
         | 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.
        
           | aeblyve wrote:
           | 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.
        
         | DontchaKnowit wrote:
         | 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.
        
       | aeblyve wrote:
       | Ray Peat PhD (RIP) and Chris Palmer MD have both emphasized the
       | role of bioenergetics in human functioning, especially brain
       | functioning.
        
       | dmitrygr wrote:
       | Metaphor taken way too far...
       | 
       | Who is the superIO chipset of the cell? Who are the VRMs?
        
         | anticensor wrote:
         | 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.
        
       | koeng wrote:
       | 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.
        
         | kridsdale1 wrote:
         | I learned some new concepts from this post. You are hereby
         | granted one hyper-upvote.
        
         | ag_rin wrote:
         | 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.
        
       | smj-edison wrote:
       | 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.
        
       | profsummergig wrote:
       | 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 West), people pretty much
       | drank water mixed with alcohol all day (to kill the germs), and
       | their food was a type of highly viscous beer (fermented liquified
       | bread).
       | 
       | - So it can't be all that simple now, can it?
        
       | peakskill wrote:
       | 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).
        
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       (page generated 2025-05-21 23:01 UTC)