Ergothioneine as a diet-derived xenobiotic: OCTN1-mediated disposition, mitochondrial redox regulation, and emerging implications for cardiovascular disease.

Abstract

Mitochondrial dysfunction is a convergent upstream driver of cardiovascular disease, linking energetic failure, oxidative stress, inflammation, and maladaptive remodelling.The inconsistent results of conventional antioxidant trials are likely to be the result of multiple factors, including compound selection, dose and timing, bioavailability, tissue delivery, patient heterogeneity, endpoint selection, baseline redox status, and interference with physiological redox signalling.Ergothioneine (EGT) is a dietary thiol/thione amino acid transported by OCTN1 and distributed between circulating and intracellular compartments. EGT could potentially impact redox mechanisms in extracellular, cytosolic, and mitochondria-related contexts; however, the precise roles of these contributions are uncertain and direct proof in cardiac mitochondria is lacking.This review evaluates cardiovascular, mechanistic, and translational evidence for EGT, separating direct cardiovascular data from non-cardiac observations and suggested mechanisms that need validation.MPST has emerged as an EGT-responsive enzyme associated with skeletal-muscle bioenergetics, but its mitochondrial, cytosolic, and cardiovascular roles remain unresolved. We also propose a putative neuro-mitochondrial framework in which EGT-mediated redox buffering may provide an adjunct to vagal anti-inflammatory signalling. However, there is no direct evidence for EGT in relation to vagal activity, α7-nAChR signalling or the cholinergic anti-inflammatory response.