4 ms·

The Excitable Mitochondria

112 points by mrkgnao 10y ago

artifaxx 10y ago
Wow, if mitochondria need to be modeled in that level of detail for accurate simulations of neurons that could be problematic. Exaflops of computational power were already the estimate just for simulating the neurons/synapses of a human brain[0], and this would increase that computational requirement orders of magnitude I imagine. Still quite fascinating. [0]http://www.riken.jp/en/pr/press/2013/20130802_1/ http://www.riken.jp/en/pr/press/2013/20130802_1/
- omgtehlion 10y ago
  Relax. No one simulates hardware down to separate electrons, the same thing applies here, I suppose. We just need to find and agree on enough high-level representation and proceed with it. P.S. that electronics CAD analogy the author used is really confusing and incorrect.
  - ChuckMcM 10y ago
    Its more the difference between a cycle accurate system simulator and a functionally accurate system simulator. Understanding the additional input from the mitochondria however might help with building more accurate FMRI type systems.
    - artifaxx 10y ago
      That is a good distinction to make, but if we don't know exactly what the cycle is things get harder to figure out. Neurons hold state and we aren't sure how much yet, let alone a deterministic method of computing it. https://www.scientificamerican.com/article/new-estimate-boosts-the-human-brain-s-memory-capacity-10-fold/ https://www.scientificamerican.com/article/new-estimate-boos...
  - artifaxx 10y ago
    I agree the CAD analogy doesn't work well here. I don't think any of us can say for sure whether or not a high level representation will need to account for such details. You are right that it might not, but it sounds like it is a possibility worth considering
rudolf0 10y ago
I don't know enough about neuroscience to determine if this is a possible genius revelation or quackery or somewhere in between. Any scientists willing to comment?
- dekhn 10y ago
  I skimmed it and figured it was quackery, but I didn't dig in deep enough to find the invalidating errors.
- abecedarius 10y ago
  I'm in the same position as you, but I checked one especially interesting claim near the beginning: "We know that organelles, such as mitochondria, are transferred from neuron to neuron. This presents a challenge to any doctrine based on discrete parts." This is supported by a ref to a paper on mitochondria being transferred from neurons to glia for autophagy, i.e. disposal. This makes the original sentence seem misleading to me, or at least lazy about finding a reference to similar transfers that are more functionally central. This makes me less interested in understanding the rest of the article.
  - Noseshine 10y ago
    I did a quick search and found this: http://physiologyonline.physiology.org/content/28/6/414 http://physiologyonline.physiology.org/content/28/6/414 > First, in vitro intercellular organelle transfer has been described in a highly diverse > assortment of cell types, including human and rodent, differentiated and multipotent, > malignant and benign, epithelial and mesenchymal, and neuronal. Thus it is safe to > conclude that the capability of one cell to donate or receive an organelle from another > cell is clearly widespread throughout mammalian cell types in culture. Stressed cells being rescued from apoptosis by organelle transfer through tunneling nanotubes (TNTs): http://www.nature.com/cdd/journal/v22/n7/full/cdd2014211a.html http://www.nature.com/cdd/journal/v22/n7/full/cdd2014211a.ht... > Further studies demonstrated that microtubule-containing TNTs were formed by stressed cells, > which had lost cytochrome c but did not enter into the execution phase of apoptosis > characterized by caspase-3 activation. Moreover, mitochondria colocalized with microtubules in > TNTs and transited along these structures from healthy to stressed cells. http://www.the-scientist.com/?articles.view/articleNo/43835/title/Mitochondria-Exchange/ http://www.the-scientist.com/?articles.view/articleNo/43835/...
undersuit 10y ago
When Hewitt started wrapping up his musings near the end I got one of those moments of clarity. I love the fairy wasps, just an ingenious technique they employ to be so small. I wrote a paper about them and xenophyophores in my 200-level Biology class. Fairy wasps discard many of their cellular machinery to maintain their small size, xenophyophores have massive redundancy of organelles and nuclei to service their absolutely massive size for a single celled organism. I am fascinated by these techniques and I made comparisons to techniques we perform in Computer Science like compiling, parallel processing, and forking. Now I discover from this article's sources that we mammals possess organelle movement that brings us closer to Multinucleate fungi. The description of the use of mitochondria by white blood cells was also fascinating. Still only understand like 20% of this article, but I'm damn interested.
Symmetry 10y ago
I suppose sharing of mitochondria would explain why the number of glial cells corresponds linearly to brain volume rather than scaling with the number of neurons. When you think about it extremely long cells like neurons do have a problem with control and intra-cellular tranfer of organelles would solve a lot of problems. I'm not at all sure about other aspects of that article but it's in the nature of man to be mistaken about some things while they are correct about others. I've also been surprised to read about genetic differences between brain cells recently that are as large as the genetic differences between immune cells and far larger than the normal sort of somatic mosaicism you get by typical errors copying that you see in other organs.
- spqr0a1 10y ago
  It's essential to the growth pattern of dendrites that neurons are able to recognize and avoid themselves. There's evidence that alternative splicing (the genetic differences you mentioned) arose in cadherins before even the immune system. Basically alternative splicing provides each neuron with a random key that has a ~1/30,000 chance of collision.
  - Symmetry 10y ago
    This gets encoded into some sort of external marker I assume?
    - spqr0a1 10y ago
      Yup, cadherins are transmembrane proteins and the variable domains are exposed on the external surface.
  - berdon 10y ago
    Out of curiosity - do you have any suggested reading to learn more about the brain at this depth?
UhUhUhUh 10y ago
Thanks so much for posting this. I've always been partial to mitochondria but that takes the cake. It's going to take me a while to digest.
jayajay 10y ago
The introduction is rather lengthy, if you're looking to skip to the part regarding mitochondria: "The Brain is What, Exactly?" section starts a bit before halfway scroll.
peter303 10y ago
Related to mitchlorians which power The Force?
tudorw 10y ago
Mitochondria are fascinating, and it seems probably very very old too! Nick Lane (http://www.nick-lane.net/ http://www.nick-lane.net/) writes a lot about the subject in; https://www.amazon.co.uk/Power-Sex-Suicide-Mitochondria-meaning/dp/0199205647 https://www.amazon.co.uk/Power-Sex-Suicide-Mitochondria-mean... https://www.amazon.co.uk/Vital-Question-Why-life-way/dp/1781250367 https://www.amazon.co.uk/Vital-Question-Why-life-way/dp/1781...

112 points by mrkgnao 10y ago

Wow, if mitochondria need to be modeled in that level of detail for accurate simulations of neurons that could be problematic. Exaflops of computational power were already the estimate just for simulating the neurons/synapses of a human brain[0], and this would increase that computational requirement orders of magnitude I imagine. Still quite fascinating. [0]http://www.riken.jp/en/pr/press/2013/20130802_1/ http://www.riken.jp/en/pr/press/2013/20130802_1/

omgtehlion 10y ago
Relax. No one simulates hardware down to separate electrons, the same thing applies here, I suppose. We just need to find and agree on enough high-level representation and proceed with it. P.S. that electronics CAD analogy the author used is really confusing and incorrect.
- ChuckMcM 10y ago
  Its more the difference between a cycle accurate system simulator and a functionally accurate system simulator. Understanding the additional input from the mitochondria however might help with building more accurate FMRI type systems.
  - artifaxx 10y ago
    That is a good distinction to make, but if we don't know exactly what the cycle is things get harder to figure out. Neurons hold state and we aren't sure how much yet, let alone a deterministic method of computing it. https://www.scientificamerican.com/article/new-estimate-boosts-the-human-brain-s-memory-capacity-10-fold/ https://www.scientificamerican.com/article/new-estimate-boos...
- artifaxx 10y ago
  I agree the CAD analogy doesn't work well here. I don't think any of us can say for sure whether or not a high level representation will need to account for such details. You are right that it might not, but it sounds like it is a possibility worth considering

rudolf0 10y ago

I don't know enough about neuroscience to determine if this is a possible genius revelation or quackery or somewhere in between. Any scientists willing to comment?

dekhn 10y ago
I skimmed it and figured it was quackery, but I didn't dig in deep enough to find the invalidating errors.
abecedarius 10y ago
I'm in the same position as you, but I checked one especially interesting claim near the beginning: "We know that organelles, such as mitochondria, are transferred from neuron to neuron. This presents a challenge to any doctrine based on discrete parts." This is supported by a ref to a paper on mitochondria being transferred from neurons to glia for autophagy, i.e. disposal. This makes the original sentence seem misleading to me, or at least lazy about finding a reference to similar transfers that are more functionally central. This makes me less interested in understanding the rest of the article.
- Noseshine 10y ago
  I did a quick search and found this: http://physiologyonline.physiology.org/content/28/6/414 http://physiologyonline.physiology.org/content/28/6/414 > First, in vitro intercellular organelle transfer has been described in a highly diverse > assortment of cell types, including human and rodent, differentiated and multipotent, > malignant and benign, epithelial and mesenchymal, and neuronal. Thus it is safe to > conclude that the capability of one cell to donate or receive an organelle from another > cell is clearly widespread throughout mammalian cell types in culture. Stressed cells being rescued from apoptosis by organelle transfer through tunneling nanotubes (TNTs): http://www.nature.com/cdd/journal/v22/n7/full/cdd2014211a.html http://www.nature.com/cdd/journal/v22/n7/full/cdd2014211a.ht... > Further studies demonstrated that microtubule-containing TNTs were formed by stressed cells, > which had lost cytochrome c but did not enter into the execution phase of apoptosis > characterized by caspase-3 activation. Moreover, mitochondria colocalized with microtubules in > TNTs and transited along these structures from healthy to stressed cells. http://www.the-scientist.com/?articles.view/articleNo/43835/title/Mitochondria-Exchange/ http://www.the-scientist.com/?articles.view/articleNo/43835/...

undersuit 10y ago

When Hewitt started wrapping up his musings near the end I got one of those moments of clarity. I love the fairy wasps, just an ingenious technique they employ to be so small. I wrote a paper about them and xenophyophores in my 200-level Biology class. Fairy wasps discard many of their cellular machinery to maintain their small size, xenophyophores have massive redundancy of organelles and nuclei to service their absolutely massive size for a single celled organism. I am fascinated by these techniques and I made comparisons to techniques we perform in Computer Science like compiling, parallel processing, and forking. Now I discover from this article's sources that we mammals possess organelle movement that brings us closer to Multinucleate fungi. The description of the use of mitochondria by white blood cells was also fascinating. Still only understand like 20% of this article, but I'm damn interested.

Symmetry 10y ago

I suppose sharing of mitochondria would explain why the number of glial cells corresponds linearly to brain volume rather than scaling with the number of neurons. When you think about it extremely long cells like neurons do have a problem with control and intra-cellular tranfer of organelles would solve a lot of problems. I'm not at all sure about other aspects of that article but it's in the nature of man to be mistaken about some things while they are correct about others. I've also been surprised to read about genetic differences between brain cells recently that are as large as the genetic differences between immune cells and far larger than the normal sort of somatic mosaicism you get by typical errors copying that you see in other organs.

spqr0a1 10y ago
It's essential to the growth pattern of dendrites that neurons are able to recognize and avoid themselves. There's evidence that alternative splicing (the genetic differences you mentioned) arose in cadherins before even the immune system. Basically alternative splicing provides each neuron with a random key that has a ~1/30,000 chance of collision.
- Symmetry 10y ago
  This gets encoded into some sort of external marker I assume?
  - spqr0a1 10y ago
    Yup, cadherins are transmembrane proteins and the variable domains are exposed on the external surface.
- berdon 10y ago
  Out of curiosity - do you have any suggested reading to learn more about the brain at this depth?

UhUhUhUh 10y ago

Thanks so much for posting this. I've always been partial to mitochondria but that takes the cake. It's going to take me a while to digest.

jayajay 10y ago

The introduction is rather lengthy, if you're looking to skip to the part regarding mitochondria: "The Brain is What, Exactly?" section starts a bit before halfway scroll.

peter303 10y ago

Related to mitchlorians which power The Force?

tudorw 10y ago

Mitochondria are fascinating, and it seems probably very very old too! Nick Lane (http://www.nick-lane.net/ http://www.nick-lane.net/) writes a lot about the subject in; https://www.amazon.co.uk/Power-Sex-Suicide-Mitochondria-meaning/dp/0199205647 https://www.amazon.co.uk/Power-Sex-Suicide-Mitochondria-mean... https://www.amazon.co.uk/Vital-Question-Why-life-way/dp/1781250367 https://www.amazon.co.uk/Vital-Question-Why-life-way/dp/1781...