The ergothioneine transporter controls and indicates ergothioneine activity — A review

Ergothioneine (ET) is a natural compound which humans and other vertebrates cannot synthesize themselves; it must be absorbed from food in which it is distributed very unevenly. In general, ET is considered an intracellular antioxidant. However, the precise physiological purpose of ET and the consequences of ET deficiency are still unclear. The ergothioneine transporter ETT (old name OCTN1; human gene symbol SLC22A4) is a powerful and highly specific transporter for the uptake of ET. Cells lacking ETT do not accumulate ET, since the plasma membrane is virtually impermeable for this hydrophilic zwitterion compound. The existence of an evolutionary conserved ergothioneine transporter implies a beneficial role for ET. ETT is the first and so far only biomarker of ET activity. Only cells with strong expression of ETT can accumulate ET to high levels. In the human body, the ability to absorb, distribute, and retain ET depends entirely on this transporter. Blockade or inactivation of ETT in animal models may be essential to at last understand the function of ET. In this review of ETT, the focus is on substrate specificity, subcellular localization, human expression profile and expression profiles across species.

► This review compiles current knowledge about the ergothioneine (ET) transporter ETT. ► Only cells with strong expression of ETT can accumulate ET to high levels. ► ETT is the first and so far only biomarker of ET activity in the human body. ► ETT effects absorption, distribution, and retention of ET in all vertebrates. ► Profiles of ETT expression across species show some dramatic differences.