New role in cells suggested for ATP
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New role in cells suggested for ATP
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Re: New role in cells suggested for ATP
#2For 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, aggregation of other proteins (protein A spurs aggregation of protein B), failure of mechanical clearance via peristaltic channels, and so forth. It's never just one thing.
Like many lines of research manage to achieve, this finding adds a little more emphasis to the need to restore mitochondrial function in the old. Clearing damaged mitochondria, delivering replacement mitochondria to cells, allotopic expression of mitochondrial genes, and so forth.
Re: New role in cells suggested for ATP
#3For 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.)
Re: New role in cells suggested for ATP
#4The subhead is more informative:
> Known as an energy carrier, molecule can also solubilize proteins
Re: New role in cells suggested for ATP
#5For 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.
Re: New role in cells suggested for ATP
#6For 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.…
You're dismissing the idea of (1) proving the "obvious" solution or disproving it via data, and you're ignoring the "how". "There are errors" doesn't say where they are errors, and how those errors translate into behavior. If the hypothesis in the source article is help up by more data, that is actually a huge deal, not just confirming something we already knew.
Re: New role in cells suggested for ATP
#7Earlier 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.…
You're dismissing the idea of (1) proving the "obvious" solution or disproving it via data, and you're ignoring the "how". "There are errors" doesn't say where they are errors, and how those errors translate into behavior. If the hypothesis in the source article is help up by more data, that is actually a huge deal, not just confirming something we already knew.
The review I shared contains many ideas along these lines. Basically the AA sequences seem to be selected to disfavor aggregation, so most mutations should increase formation:
>"Many of the characteristics of proteins that enable the avoidance of aggregation, and amyloid formation in particular, are encoded by their amino acid sequences116. The elucidation of this code has enabled the identification of factors that determine the intrinsic aggregation propensity of these molecules117–119. Hence, it has been realized that globular proteins fold into structures that sequester aggregation-prone regions in their interior; in addition, typical features of the folding process, such as very high cooperativity, generate considerable kinetic barriers to the conversion of folded proteins into aggregation-prone species50,120. Furthermore, specific patterns of residues, such as alternating hydrophobic–hydrophilic stretches50,121, that tend to favour the amyloid state are commonly selected against during evolution119,121,122 or are otherwise neutralized by the insertion of highly aggregation-resistant residues, which are known as ‘gatekeepers’ (REFS 50,123)."
Really I doubt in the end there will be any disease not associated with amyloid/aggregate formation.
Re: New role in cells suggested for ATP
#8While 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 high concentrations in cells.
Sure it's important for neurons to prevent amyloid-beta from aggregating, but we can explain why neurons have a super high (mM) ATP concentration for two other good reasons:
1. Unlike other cells, neurons conduct electrical signals. Every time a neuron fires it opens channels that allow sodium and potassium to flow through the membrane. Then, it needs to get those ions back across the membrane so the neuron can keep functioning. To do this neurons make prodigious use of Na/K-ATPase pumps, that exchange intracellular Na for extracellular K, against an electrochemical gradient. This is active transport that requires tons of ATP. In a typical animal cell active transport is a relatively small (~1/10th) portion of cellular energy expenditure compared to neurons (~7/10th).
2. ATP is used in actin filament polymerization. Each molecule of filamentous actin is coupled to an ATP molecule, and actin is found in neurons at mM concentrations. Actin is a major structural protein in cells, and plays a particularly important role in neurons. Actin helps create filopodial protrusions; if you compare a neuron to another type of cell you can immediately tell it's a protrusion machine. Even these protrusions (axons and dendrites) have protrusions (neurites and dendritic spines) that are constantly reorganizing to allow for structural plasticity among the brain's neural network connections. One of my dissertation projects was to simulate actin activity in neurons; for anyone's interested, here are some pretty neat visuals of this...
Actin polymerization to create a dendritic spine: https://youtu.be/JH-hGjzhEFQ
Small segment of a dendrite with surface receptor diffusion: https://www.youtube.com/embed/6ZNnBGgea0Y
Creating dendritic meshes in python: https://youtu.be/tDKUU0SqbSA
Re: New role in cells suggested for ATP
#9For 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.)
[deleted]
Re: New role in cells suggested for ATP
#10For 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.…
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?
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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 minute.