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New role in cells suggested for ATP

cen.acs.org

11–19 of 19 posts

Re: New role in cells suggested for ATP

#11

For broader context, this might be used to help explain the well known link between the age-related decline in mitochondrial function (and consequence lowered production rate of ATP) and the age-related development of aggregates such as amyloids and tau. Aggregates are age-related, but one needs explanations as to why that is the case. Other proximate causes include declining cellular garbage collection mechanisms, a…

Would it be encouraging to see if amyloid plaques dissolve in a concentrated aqueous solution of ATP? (Sorry if nonsensical. I am approaching the topic as a layman.)

Had a different response here before but this quote from the article suggests maybe!

"ATP kept proteins in boiled egg white from aggregating."

It also appears the concentrations they're talking about are quite reasonable (10mM or so).

That said, once an aggregate is formed you usually need pretty heroic methods to solubilize it. Much stronger detergents and denaturants at higher must be used, and in those cases you run into other problems.

After solubilizing the aggregate, you have to fold the individual proteins back up. But now you have to do it in an environment where you 1.) a molecule that keeps the protein unfolded and 2.) a ton of other unfolded proteins around. You could slowly get rid of 1.) by dialysis or something similar. But when you have a bunch of unfolded proteins hanging around together, you almost always get aggregates.

In practice, it's quite unlikely that ATP concentrations high enough to unfold an aggregate wouldn't unfold all sorts of other things. This would also mean the stuff you need to keep the rest of the cell working... so from a practical perspective this is unlikely to work.

Re: New role in cells suggested for ATP

#12
post #5

Earlier quoted context omitted.

>"Aggregates are age-related, but one needs explanations as to why that is the case." I don't think there is much mystery here. As cells divide they accumulate (genetic, and other types of) errors. One thing that happens is proteins/peptides are more likely to end up in their most thermodynamically stable state, since it requires constant maintenance to avoid it. http://www.nature.com/nrm/journal/v15/n6/full/nrm3810.…

So given that neurons almost never divide (1), and other cell types like skin cells divide every few hours (2), based on your formulation how do we explain that we never find A-beta plaques in skin cells? ---- 1. It was thought that adult neurons didn't divided at all until like 1998; now we know some new neurons are produced from progenitor sources at very low rates. 2. 30,000 to 40,000 skin cells are produced every…

What matters is how many divisions away from the fertilized egg. The "mainstream" idea has lead to many paradoxes: https://www.ncbi.nlm.nih.gov/pubmed/25459141

Re: New role in cells suggested for ATP

#13

While ATP may help to solubilize proteins, I don't find it surprising the cells under question have very high ATP concentrations. I take issue with this statement: > In addition to being an energy source for biological reactions, for which micromolar concentrations are sufficient, we propose that millimolar concentrations of ATP may act to keep proteins soluble. This may in part explain why ATP is maintained in such…

I concur. To keep a neuron happy requires large amount of energy and ATP. Every electrophysiologist would know this from the very beginning.

Re: New role in cells suggested for ATP

#14

While ATP may help to solubilize proteins, I don't find it surprising the cells under question have very high ATP concentrations. I take issue with this statement: > In addition to being an energy source for biological reactions, for which micromolar concentrations are sufficient, we propose that millimolar concentrations of ATP may act to keep proteins soluble. This may in part explain why ATP is maintained in such…

Guessing this is a major reason that "big" brains are extremely rare. There's strong selective pressure against such an energy hungry organ and most of benefits (ooh, we can discuss issues on HN) don't accrue until much later. ;-)

Re: New role in cells suggested for ATP

#15
post #5

For broader context, this might be used to help explain the well known link between the age-related decline in mitochondrial function (and consequence lowered production rate of ATP) and the age-related development of aggregates such as amyloids and tau. Aggregates are age-related, but one needs explanations as to why that is the case. Other proximate causes include declining cellular garbage collection mechanisms, a…

>"Aggregates are age-related, but one needs explanations as to why that is the case." I don't think there is much mystery here. As cells divide they accumulate (genetic, and other types of) errors. One thing that happens is proteins/peptides are more likely to end up in their most thermodynamically stable state, since it requires constant maintenance to avoid it. http://www.nature.com/nrm/journal/v15/n6/full/nrm3810.…

I don't think that necessarily explains how an offspring resets all of that. By that same logic, there should be a limit to how many generations of human there are.

Re: New role in cells suggested for ATP

#17
post #5

Earlier quoted context omitted.

>"Aggregates are age-related, but one needs explanations as to why that is the case." I don't think there is much mystery here. As cells divide they accumulate (genetic, and other types of) errors. One thing that happens is proteins/peptides are more likely to end up in their most thermodynamically stable state, since it requires constant maintenance to avoid it. http://www.nature.com/nrm/journal/v15/n6/full/nrm3810.…

I don't think that necessarily explains how an offspring resets all of that. By that same logic, there should be a limit to how many generations of human there are.

Apparently there are about 7 million oocytes created per generation[1], which could be done in 23 divisions: 2^23 = 8,388,608

So first, it doesn't require that many divisions per generation of human. Second, there are "errors" that get passed on to the offspring. Third, a lot of selection goes on so that only fertilized eggs without huge issues will eventually be born.

[1] https://en.wikipedia.org/wiki/Oogenesis

Re: New role in cells suggested for ATP

#18
post #17

Earlier quoted context omitted.

I don't think that necessarily explains how an offspring resets all of that. By that same logic, there should be a limit to how many generations of human there are.

Apparently there are about 7 million oocytes created per generation[1], which could be done in 23 divisions: 2^23 = 8,388,608 So first, it doesn't require that many divisions per generation of human. Second, there are "errors" that get passed on to the offspring. Third, a lot of selection goes on so that only fertilized eggs without huge issues will eventually be born. [1] https://en.wikipedia.org/wiki/Oogenesis

Right, but it would seem like many such strategies could be applied to somatic cells. And we also know that there are complex organisms that don't meaningfully age.

Re: New role in cells suggested for ATP

#19
post #17

Earlier quoted context omitted.

Apparently there are about 7 million oocytes created per generation[1], which could be done in 23 divisions: 2^23 = 8,388,608 So first, it doesn't require that many divisions per generation of human. Second, there are "errors" that get passed on to the offspring. Third, a lot of selection goes on so that only fertilized eggs without huge issues will eventually be born. [1] https://en.wikipedia.org/wiki/Oogenesis

Right, but it would seem like many such strategies could be applied to somatic cells. And we also know that there are complex organisms that don't meaningfully age.

See my earlier reference here regarding somatic cells (they don't require so many divisions either): https://news.ycombinator.com/item?id=14397992

What organisms are you talking about that don't meaningfully age?

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