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...
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