Speculation on a Role for ATP in Age-Related Protein Aggregation

Researchers here suggest that ATP, the chemical energy store molecule produced by mitochondria, also serves to keep proteins soluble in the cell. This might help to explain the well known correlation between age-related mitochondrial dysfunction and age-related neurodegenerative diseases involving protein aggregates that build up in brain tissue. If mitochondria are producing less ATP, that may in turn accelerate the seeding of solid aggregates, and the consequent harm they produce. At this stage, the research is interesting but still fairly speculative when it comes to the degree to which this chemistry is relevant in disease states, however.

Adenosine triphosphate (ATP) performs many jobs in a cell. It carries energy, serves as a signaling molecule, and is the source of adenosine in DNA and RNA. But cells contain far more ATP than these known uses seem to require. That might be because ATP also can solubilize proteins, suggests a new study.

ATP has the general characteristics of a hydrotrope, an amphiphilic molecule that has both a hydrophilic and a hydrophobic component but does not assemble into structures such as micelles. Hydrotropes are used industrially to solubilize hydrophobic species in aqueous solution. The hydrophobic portion of hydrotropes - such as ATP's adenosine - likely interacts with the hydrophobic species, while the hydrophilic part - such as ATP's triphosphate - allows the species to stay in solution.

In the new work, a team investigated the effects of ATP on the aggregation of several proteins. They found that ATP could prevent the aggregation of two proteins known to form amyloid clumps. For a third protein, ATP was further able to dissolve fibers of already aggregated protein. And ATP kept proteins in boiled egg white from aggregating. "Most healthy cell functions require that proteins remain soluble at enormous intracellular concentrations, without aggregating into pathogenic deposits. The cell may exploit a natural hydrotrope to keep itself in a functioning, dynamic state."

Link: http://cen.acs.org/articles/95/i21/New-role-cells-suggested-ATP.html

Comments

Yes that means NAD is linked to this process too. Not really a surprise and makes Sinclairs work even more relevant.

Posted by: Steve Hill at May 25th, 2017 7:44 AM
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