Dodecanedioic Acid: Alternative Carbon Substrate or Toxic Metabolite?

Twelve-carbon dicarboxylic acid dodecanedioic acid (DODA) has gained recent interest as an alternative nutrient. However, little is known about DODA cellular metabolism. Our study presents novel data on DODA metabolism and its potential role as an alternative carbon substrate. Cells are readily oxidizing DODA as a primary carbon source, yielding acetyl-CoA and succinate and replenishing the Krebs cycle. Furthermore, cells treated with DODA are characterized by a distinct metabolic profile, whereas pathways associated with energy metabolism are highly impacted. We also found that DODA administration alters carbon substrate preferences for respiration, restricting overreliance on one substrate as a primary fuel. Consequently, by rebalancing cellular energy metabolism, DODA as a supplemental carbon source may have significant therapeutic implications in conditions that are characterized by energy deficiency and metabolic inflexibility.