
Mitochondria may hold keys to anxiety and mental health - jger15
https://www.quantamagazine.org/mitochondria-may-hold-keys-to-anxiety-and-mental-health-20200810/
======
wombatmobile
> 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."

~~~
msla
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](https://en.wikipedia.org/wiki/Lynn_Margulis)

~~~
wombatmobile
The complication with (incorrectly) labeling Margulis "an AIDS denialist",
msla, is that you then make her responsible for a whole collection of
unsubstantiated tropes that are targeted by that label. That's unwarranted,
because Margulis was doing something quite opposite to "AIDS denialism";
Margulis, an esteemed scientist, was proposing an alternative causative factor
that may explain AIDS, which isn't HIV, or more precisely, which isn't HIV in
isolation.

This fascinating discussion will make your jaw drop
[https://www.discovermagazine.com/the-sciences/discover-
inter...](https://www.discovermagazine.com/the-sciences/discover-interview-
lynn-margulis-says-shes-not-controversial-shes-right)

~~~
msla
> Margulis, an esteemed scientist, was proposing an alternative causative
> factor that may explain AIDS, which isn't HIV, or more precisely, which
> isn't HIV in isolation.

She's not esteemed in the field of what causes AIDS. She's esteemed in a
different sub-field. In terms of AIDS, the actual _experts_ have come to the
conclusion she's wrong, and one thing we should all have learned by now is
that our ignorance is not equal to the knowledge of experts.

> This fascinating discussion will make your jaw drop

Not for the reasons you think it would, though.

~~~
coldtea
> _She 's not esteemed in the field of what causes AIDS. She's esteemed in a
> different sub-field. In terms of AIDS, the actual experts have come to the
> conclusion she's wrong, and one thing we should all have learned by now is
> that our ignorance is not equal to the knowledge of experts._

The history of science also told us by now that experts are stubborn, and
sometimes they have to first die, for the next generation to accept another
theory.

It has also taught us that important new discoveries more often than not come
not from established experts in a field, but by people from another sub-field
or another field all together...

It has also taught us that scientists should continue challenging prevailing
hypotheses all the time, because that's part and parcel of doing science...

~~~
jkhdigital
Exactly. An “expert” is a skilled practitioner of some domain of human
endeavor; a scientist is a truth-seeker. Expertise is orthogonal to scientific
truth.

~~~
msla
> Expertise is orthogonal to scientific truth.

Expertise is the result of successful scientific seeking.

------
podgaj
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
> 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.

~~~
podgaj
This is pretty much all you need to know:

[https://ubiquinol.org/sites/default/files/statins.gif](https://ubiquinol.org/sites/default/files/statins.gif)

The thinking on cholesterol and heart disease is changing rapidly and there
really is no strong evidence high cholesterol before a heart attack leads to
any bad outcomes. After a heart attack, statins are ok.

But like we see, side effects. My doc wanted me on them but they gave my
mother horrible myopathy so I passed. My HDL was really low until I took out
all plant oils and eat fats pretty much only from fish and olive oil. Now my
HDL in mid range normal. This is becasue the omega 3 helps with reverse
cholesterol transport.

But again, this is me and my genetics. We have Saami (Inuit) heritage which is
why I think i need this diet.

------
tgv
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
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/](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
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?”

~~~
DoofusOfDeath
I recall a similar story regarding (iirc) programming language type theory:
"How does it handle recursion?"

------
vwat
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/](http://naviauxlab.ucsd.edu/science-item/autism-research/)

~~~
fasteo
>>> obscure drug that blocks ATP receptors

In case you are wondering, Suramin[1] is the drug

[1]
[https://en.wikipedia.org/wiki/Suramin](https://en.wikipedia.org/wiki/Suramin)

------
sradman
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/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901651/)

------
WantonQuantum
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
Ha.. my mom is super anxious as was her mom.. and me.. yep!

~~~
WantonQuantum
Yes, I definitely got my depression from my mother's side of the family. But
as far as I'm aware, after controlling for environmental factors (such as
amount of time spent with each parent, etc) there's no detectable bias toward
maternal inheritance.

------
koeng
Fun fact: we still can’t genetically transform human mitochondria, and we’ve
tried for _decades_

~~~
peteretep
What would it mean to “genetically transform” a human mitochondria, and why
are have we been trying to for decades?

~~~
koeng
Add new DNA into the human mitochondria. If you could do that, you unlock a
massive amount of science around how mitochondria function, kinda similar to
“what I cannot create I do not understand.

From an engineer’s perspective, mitochondria are kinda the equivalent to
virtual machines running on normal computers, as little “virtual cells” within
cells. Their genomes are so stripped down that you can do some wild things
with them.

~~~
est31
> If you could do that, you unlock a massive amount of science around how
> mitochondria function

Note that 99% of the proteins contained in mitochondria are [coded] in the
nucleus, only 1% is [coded] in the mitochondrial chromosome. It's extremely
small, only containing 37 genes of which most are related to translation (but
of course translation requires far more, e.g. elongation factors).

[https://www.nature.com/articles/nrm2959](https://www.nature.com/articles/nrm2959)

~~~
reubenswartz
I get what you're saying, but I think you have a typo in there. Most of the
proteins in the mitochondria are coded by nuclear DNA, but the proteins
themselves end up in the mitochondria.

~~~
est31
Thanks! Edited.

------
Symmetry
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.

~~~
reubenswartz
Yes and his book "The Vital Question", which covers some of the same ground.
Highly recommend.

------
zwkrt
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.

~~~
Kaze404
I don't understand the connection.

~~~
rexpop
Although "all experience hath shewn that mankind are more disposed to suffer,
while evils are sufferable, than to right themselves by abolishing the forms
to which they are accustomed," organisms have been known to alter our
environments to suit our needs, rather than suffer them even to our deaths.
For example, when it rains I often open an umbrella.

Perhaps with the right anti-depressant cocktail, I wouldn't bother.

~~~
wahern
Based on what I've seen in nature films regarding how great apes (chimpanzees,
orangutans, etc) react to rain, and the extreme aversion to being rained on
that I've anecdotally seen in several different cultures, I have a suspicion
that an aversion to rain--particularly to unwanted/unexpected rain--might be
not only instinctual but peculiar and specific, similar to our aversions to
spiders and snakes. Or maybe not, but it has definitely stood out to me.

------
nayeem-rahman
the power house of the cell

~~~
Terr_
Exactly what I thought of when they said:

> “They’re the chief executive organelle of the cell.”

Which IMO sounds odd, given that Mitochondria are seldom described as having
much "decision making" power.

~~~
Symmetry
Well, they do start the process of triggering apoptosis or cell suicide, for
instance.

------
techbio
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.

------
dr_dshiv
Here is one of my favorite videos of mitochondrial transport, in vivo:
[https://www.youtube.com/watch?v=x5IxkI6tkn0](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?)

------
starfallg
> 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.

------
itsmarsu
Assuming the title is true, that'd make mitochondria the powerhouse of the
self.

------
myvii
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).

------
thelazydogsback
I recommend this book:

"Mitochondria and the Future of Medicine: The Key to Understanding Disease,
Chronic Illness, Aging, and Life Itself"

\-- by Lee Know

[https://www.amazon.com/gp/product/1603587675](https://www.amazon.com/gp/product/1603587675)

~~~
rl3
> _Lee Know, ND, is a licensed naturopathic doctor based out of Canada, and
> the recipient of several awards. Known by his peers to be a strategic and
> forward-thinking entrepreneur and researcher, he has held positions as
> medical advisor, scientific evaluator, and director of research and
> development for major organizations. Besides managing Scientific Affairs for
> his own company, he also currently serves as a consultant to the natural-
> health-products and dietary-supplements industries, and serves on the
> editorial advisory board for Canada 's most-read natural health magazine._

At least he's honest about his lack of medical expertise and conflict of
interest.

~~~
thelazydogsback
And? Do you have any particular problems with any actual insights in the book?
Do you think the medical industry is forward-thinking or adverse to new ways
of thinking in general? I don't want this guy removing my appendix, but there
are many cases of people outside or peripheral to a domain without
qualifications that make a huge impact on a particular area and lead the way
for more research -- and we are all aware of the medical establishment's lack
of proper training when it comes to nutrition.

~~~
rl3
The problem I have is they're attempting to sound authoritative via way of
medical and scientific expertise while in fact having none, in addition to
having a financial interest in pushing supplements. It severely impugns the
credibility of the book.

> _Do you think the medical industry is forward-thinking or adverse to new
> ways of thinking in general?_

Both. It's so vast that sweeping generalizations don't really apply.

> _... but there are many cases of people outside or peripheral to a domain
> without qualifications that make a huge impact on a particular area and lead
> the way for more research ..._

Sure, but an ND with ties to the supplement industry ain't that.

> _... and we are all aware of the medical establishment 's lack of proper
> training when it comes to nutrition._

You could even argue the medically-recommended low-fat diet craze was one of
the largest health disasters in modern history. Unfortunately it doesn't make
this guy any more correct or rigorous in his opinions.

Please understand this isn't a personal attack. I take supplements and
aggressively fast every day precisely because I largely believe in the
mitochondrial theory of aging. For all I know, everything in the book could be
factually correct and not misconstrued. It doesn't change the fact the author
is presenting themselves as a medical expert.

------
m0zg
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.

------
hoka-one-one
Ok Ray Peat

------
layoutIfNeeded
Hm, but I was told it’s only in my head!

------
peteretep
Completely left-field comment:

> Carmen Sandi recalls the skepticism she faced at first. A behavioral
> neuroscientist at the Swiss Federal Institute of Technology in Lausanne, she
> had followed a hunch

I feel like people use “radical ideas” like this to justify whatever their
bullshit of the day is, and generally ignore the fact that they almost always
come from experts in their respective fields.

