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Mitochondria may hold keys to anxiety and mental health

277 points| jger15 | 5 years ago |quantamagazine.org | reply

161 comments

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[+] wombatmobile|5 years ago|reply
> The organelles are ancient invaders — the remnants of symbiotic bacteria that integrated themselves into host cells about 2 billion years ago and specialized for energy production.

That's accepted as scientific orthodoxy now, but it wasn't always. In the 1960's, evolutionary biologist Lyn Margulis proposed the theory that cell organelles such as mitochondria and chloroplasts were once independent bacteria, which combined through symbiotic mergers of bacteria to evolve into eukaryotic cells. Ernst Mayr called this "perhaps the most important and dramatic event in the history of life".

Throughout her career, Margulis' work could arouse intense objection. One grant application elicited the response, "Your research is crap, do not bother to apply again", and her formative paper, "On the Origin of Mitosing Cells", appeared in 1967 after being rejected by about fifteen journals.

In 2002, Discover magazine recognized Margulis as one of the 50 most important women in science.

In 1995, Richard Dawkins said, "I greatly admire Lynn Margulis's sheer courage and stamina in sticking by the endosymbiosis theory, and carrying it through from being an unorthodoxy to an orthodoxy. I'm referring to the theory that the eukaryotic cell is a symbiotic union of primitive prokaryotic cells. This is one of the great achievements of twentieth-century evolutionary biology, and I greatly admire her for it."

[+] amelius|5 years ago|reply
How is the research going on the effects of antibiotics on these organelles?
[+] msla|5 years ago|reply
She's a victim of Nobel Disease and said stupid things out of her field. How is that controversial?
[+] msla|5 years ago|reply
Sadly, these days Lynn Margulis is better known for her AIDS crankery:

> Margulis said that "the set of symptoms, or syndrome, presented by syphilitics overlaps completely with another syndrome: AIDS," and also noted that Kary Mullis[a] said that "he went looking for a reference substantiating that HIV causes AIDS and discovered, 'There is no such document.' "

> This provoked a widespread supposition that Margulis had been an "AIDS denialist." Notably Jerry Coyne reacted on his Why Evolution is True blog against his interpretation that Margulis believed "that AIDS is really syphilis, not viral in origin at all."[50] Seth Kalichman, a social psychologist who studies behavioral and social aspects of AIDS, cited her 2009 paper as an example of AIDS denialism "flourishing",[51] and asserted that her "endorsement of HIV/AIDS denialism defies understanding."[52]

Also: 9/11 crankery!

> Margulis argued that the September 11 attacks were a "false-flag operation, which has been used to justify the wars in Afghanistan and Iraq as well as unprecedented assaults on ... civil liberties." She claimed that there was "overwhelming evidence that the three buildings [of the World Trade Center] collapsed by controlled demolition."[5]

https://en.wikipedia.org/wiki/Lynn_Margulis

[+] podgaj|5 years ago|reply
I am disabled with Anxiety and Mood Disorder and chronic fatigue/depression. Typical "Bipolar" presentation. It runs in my family on my mothers side. We also have a history of early (45 years old) heart disease.

So I knew this was mitochondrial but it was revealed when I received my genome. We have issues with our electron transport chain; Complex I (ND1 and ND4) and Complex III (MT-CYB).

So diet and lifestyle was crucial in getting me off all of my meds, and I was on a lot. High dose riboflavin was a huge help.

Getting complex I to work well helps with the heart since it increases NAD. Also getting enough ubiquinone from diet helps. I get it mostly from seafood like Salmon and Liver. I might try and take a CoQ10 supplement soon. But the fact that we make it endogenously makes me think it is not needed. Statins will stop the production of CoQ10 by lowering FPPP production which is why they fail to help people with Heart Disease.

Balancing the flow and the oxidative stress from the mitochondrial electron transport chain is crucial.

[+] slfnflctd|5 years ago|reply
> Statins will stop the production of CoQ10 by lowering FPPP production which is why they fail to help people with Heart Disease

I would like to know more about this. I've been on a statin for several years and feel like my energy has dropped through the floor in that time. I also feel like I have a 'statin hangover' when I wake up in the morning (I usually take it with my supper). This could all be correlation, and aside from cholesterol levels I haven't been diagnosed with heart disease. But I would like to know more, because I hate taking this stuff and really don't like the idea of being on it the rest of my life.

[+] pete762|5 years ago|reply
> I am disabled with Anxiety and Mood Disorder and chronic fatigue/depression. Typical "Bipolar" presentation. It runs in my family on my mothers side.

That sounds awfully familiar. Would you be so kind to provide any starting point to begin research into this, including the supplement stuff you mentioned afterwards?

[+] tahoeskibum|5 years ago|reply
I'm in a similar situation. I've found that taking CoQ10 and NAD+ (e.g. Niagen or Elysium Basis) has been helpful.
[+] tokai|5 years ago|reply
Did you ever take lithium?
[+] tgv|5 years ago|reply
The article does not really warrant the title. The best evidence seems to be "a meta-analysis of 23 studies on mitochondria and anxiety: 19 demonstrated “significant adverse effects of psychological stress on mitochondria”", but that's the other way around. And there are of course many factors associated with anxiety and other mental health issues that do not seem related to mitochondria.

Nobody is going to deny that a badly functioning component in your body can affect your mental health, and some of the mechanisms sound interesting, but not enough to call mitochondria the "key to anxiety and mental health". It's more like: an easily overlooked factor that can contribute.

[+] aantix|5 years ago|reply
I'm surprised that the role of Magnesium isn't discussed as well.

"Mitochondrial Mg2+ homeostasis decides cellular energy metabolism and vulnerability to stress"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960558/

Anecdotally, I've been taking Magnesium l-threonate and it's probably the least anxious I've ever been in my entire life (I'm 42).

The only thing comparable was Lexapro, but I always had a love/hate relationship because of the side effects.

[+] scrozier|5 years ago|reply
Your opening line made me laugh inappropriately. When I was in grad school in molecular biophysics, someone asked, “if I fall asleep during a talk, and wake up just in time for questions, what question can I ask, to look smart, regardless of the topic of the talk?” The answer? “What was the magnesium concentration?”
[+] treeman79|5 years ago|reply
Magnesium is amazing for many things.

Have several crippling conditions. Magnesium has brought drastic relief.

Muscle aches, migraines, cognitive issues.

Al much improved.

[+] claytoneast|5 years ago|reply
Which product specifically do you use, if you don't mind me asking? I'd like to try it myself to see if it helps me as well.
[+] fasteo|5 years ago|reply
Note that Magnesium deficiency might be a downstream effect of a malfunctioning mitochondria [1]. Taking CoQ10 might help (it did greatly in my case)

  The authors findings demonstrate low brain free [Mg2+] in our patients and indicate that it resulted from failure of the respiratory chain.
[1] https://journals.sagepub.com/doi/pdf/10.1097/00004647-199905...
[+] myvii|5 years ago|reply
Magnesium L-threonate may have better cognitive than other formulations, but I wonder if a magnesium glycinate formulation would be better for anxiety/stress reduction.

Anectdotally also, I take Magnesium Bisglycinate from Thorne occasionally and it helps me relax and feel less anxious. My muscles stay pretty rigid normally and after taking the magnesium supplement I can feel everything loosen up. Helps with sleep too.

[+] sevencolors|5 years ago|reply
The article noted that Acetyl-L-Carnitine

> protected mice vulnerable to behaviors associated with depression in humans

Which I'm curious about as well.

[+] podgaj|5 years ago|reply
Magnesium will reduce ATP Since it is a cofactor for the ATPases. Less ATP means less anxiety.
[+] jadbox|5 years ago|reply
What dosage do you take? I've had some results with Magnesium Citrate.
[+] wolco|5 years ago|reply
I heard threonate crosses the brain blood barrier. I was worried about the opposite happening. What brand do you take?
[+] MattRix|5 years ago|reply
How long did you have to take it before you noticed a difference? Are we talking one per day?
[+] vwat|5 years ago|reply
This guy theorized that autism is caused by a problem with ATP and mitochondria. He did a trial of an old, obscure drug that blocks ATP receptors (for signaling, not metabolism) on young ASD patients and there was noticeable improvement in their symptoms. More studies are underway.

http://naviauxlab.ucsd.edu/science-item/autism-research/

[+] sradman|5 years ago|reply
For those, like me, who find this article too pseudo-sciencey, the paper Psychological Stress and Mitochondria: A Conceptual Framework [1] lays the foundation I was missing:

> It is also interesting to note in the context of stress regulation that all steroid hormones, including glucocorticoids and sex hormones, are synthesized in a process that is regulated by, and occurs in mitochondria, further linking mitochondrial biology to stress signaling.

Stress in this sense refers to all biological stressors such as physical exertion. Mitochondria, therefore, are not only central to energy production but also to stress response. This is simply how the system works.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901651/

[+] WantonQuantum|5 years ago|reply
Presumably it's not the mitochondrial DNA itself that is causing the problem but rather chromosomal DNA (or some combination). If it were only mitochondrial DNA then it would be strongly heritable from the mother's side, which is not what we see.
[+] sjg007|5 years ago|reply
Ha.. my mom is super anxious as was her mom.. and me.. yep!
[+] koeng|5 years ago|reply
Fun fact: we still can’t genetically transform human mitochondria, and we’ve tried for decades
[+] Symmetry|5 years ago|reply
Mitochondria are really one of our cells' most under appreciated organelles and the consequences of them being "the powerhouse" are a lot more profound than you might think. I highly recommend Nick Lane's book on them, Power, Sex, Suicide: Mitochondria and the meaning of life, which explores the consequences of the biochemistry, population genetics, of mitochondria for how animals live in general. It's far more interesting than biochemistry has any right to be, along with his other books.
[+] zwkrt|5 years ago|reply
One day we will have a full biological understanding of anxiety and mental health, at which point people will no longer need to change the world around them.
[+] rexpop|5 years ago|reply
There is a recent thread on how even CBT (Cognitive Behavioral Therapy) is akin to wire-heading[0], and we've known for ages that loneliness encourages depression and addiction[1] so it's not a far leap to suggest that adverse environmental conditions can be measurably, significantly even fatally unpleasant. I think this conclusion is also common knowledge, intuitively accessible to any observant adult. It's strange, then, that we spend so much time addressing the chemical conclusions at which individuals arrive by virtue of their social relations. I suspect there are political reasons behind the medicalization of depression. Why should my neurochemistry be held responsible for relations whose creature I socially remain?

0. https://twitter.com/buss_patriarchy/status/12890769568734658...

1. https://www.youtube.com/watch?v=C8AHODc6phg

[+] ineedasername|5 years ago|reply
That implies that all efforts to change external circumstances are linked to mental health issues.

Also understanding does not automatically lead to fixing. We understand a lot of things that we haven't been able to change. And what if the understanding we gain shows us that the causes of our anxiety and mental health issues are things in the world around us?

[+] InfiniteRand|5 years ago|reply
With anxiety borne from mental illness, at least in my experience, I cannot be sure if the anxiety I feel is more related to my internal state or external state. For instance, on a day when I am doing good, I eat a delicious meal, I am happy with it, on a day when I am doing bad, I eat a delicious meal I focus on the calories and my overall diet and my weight, etc.

In theory at least, with perfect mental health I will be able to confidently relate my feelings to the external world and be able to reason about changing the external world to deal with real anxieties rooted in perceptions of real danger.

I think for people who suffer from mental illness related to anxiety, or at least for me, the goal is not to completely eliminate anxiety but to be able to know that the anxiety I feel is reasonable and appropriate. (Similarly for my chronic depression)

Of course the line between reasonable and unreasonable anxiety is not always clear. The far points are clear, being anxious about some stranger approaching you with a gun, that's reasonable, being unable to get out of bed because you are certain everything is going to go wrong no matter what, that is unreasonable. But should you be anxious about this person because you did that thing but you have a history with this person and... that sort of thing is fuzzy.

[+] treeman79|5 years ago|reply
Emotional trauma can trigger some serious mental illness. Some events change a personality forever.
[+] podgaj|5 years ago|reply
AHAHHHAA! I love this! being a Daoist and an old Buddhist, this understanding helped me so much with my OCD/Anxiety.
[+] Kaze404|5 years ago|reply
I don't understand the connection.
[+] newforms|5 years ago|reply
It may be the case that the greater understanding will lead to a greater need for change.
[+] techbio|5 years ago|reply
Realizing mitochondria were the "powerhouse" due to a voltage gradient created by chemically transforming ATP to ADP across a membrane gave me a eureka moment about how small such a mechanism can be, and how powerful in great numbers.
[+] starfallg|5 years ago|reply
> In 1924, this man Boris Mikhaylovich Kozo-Polyansky wrote a book called Symbiogenesis: A New Principle of Evolution, in which he reconciled Darwin’s natural selection as the eliminator and symbiogenesis as the innovator.

TIL that evolution is a GAN.

[+] dr_dshiv|5 years ago|reply
Here is one of my favorite videos of mitochondrial transport, in vivo: https://www.youtube.com/watch?v=x5IxkI6tkn0

Apparently, there is a whole economy for transporting microchondria within dendrites. More mitochondria in an area of the dendrites allows for faster growth and responsiveness to input.

(There is another time-lapse video I've seen before of mitochondrial transport, but I'm frustrated that my own browsing history isn't making it easier to find. Are there tools that help make ones own browsing history more useful/accessible?)

[+] itsmarsu|5 years ago|reply
Assuming the title is true, that'd make mitochondria the powerhouse of the self.
[+] myvii|5 years ago|reply
I wonder if there's a connection to Nicotinamide Riboside (NR) supplementation.

NR is a precursor to NAD+, which has been shown to improve mitochondrial function especially under stress.

NAD+ is one of those molecules used in a ton of metabolic processes and over a lifespan NAD+ avalability declines. This decline is linked to numerous age-related diseases. There's a bit of research showing NAD+ supplementation contributes to anti-aging effects.

NR is easy to take, well-tolerated, and a cheap precursor for NAD+. There are IV clinics that have NAD+ infusions, but they cost like $500. On the other hand, you can get a month's supply of NR for around $50 (Thorne's ResveraCel).

[+] m0zg|5 years ago|reply
Whenever I see "X may hold keys to Y", I always augment it with "or it may not". In fact "may not" is the more likely outcome because if it did come anywhere close to "holding" the keys the headline would be affirmative.

It's a variant of Betteridge's law, if you will.