An interesting paper was published recently. Intracellular metabolic gradients dictate dependence on exogenous pyruvate This was from the same lab as the excellent paper A non-canonical tricarboxylic acid cycle underlies cellular identity . An interesting question that the paper answers is what drives the need for external pyruvate. The paper concludes "The requirement for pyruvate over lactate can be partially rescued by NAD+, suggesting that at least part of the role of pyruvate in development is regulation of cellular redox62. ". What I find particularly interesting about the link to NAD+ is that Complex 1 (which is reduced in stem cells) has a major role in maintaining NAD+ levels. Hence if it is to be inhibited in some form then something else needs to be done to maintain NAD+ levels. Although Complex 1 maintains mitochondrial NAD+ rather than cytosolic NAD+, depletion in the Mitochondria will block the Malate-Aspartate shuttle affecting the cytosol Pyruvate in th...
Recently another paper was produced which hinted at a link between mitochondrial DNA damage and aging. In fact I have been of the view for some time that the damage to mitochondrial DNA is what drives both aging and development at the lowest level. I have said this before, but thought a summary would be useful. It is worth, however, explaining a few terms first before going into the details of how this happens. It is well known that animals (including people) are made of large number of cells. Within those cells there are little "organelles" called mitochondria that are used to convert nutrients into ATP (Adenosine Tri Phosphate) which is used by cells as a form of energy. There is a hypothesis that is generally believed to be true that this structure of cells arose from some bacteria going into old cells called archea as it created a form of symbiosis where the larger cells provided nutrients to the bacteria for the bacteria to process those. This is called Endosymbio...