| First Author | Sprenger HG | Year | 2025 |
| Journal | Cell Metab | Volume | 37 |
| Issue | 4 | Pages | 857-869.e9 |
| PubMed ID | 39965563 | Mgi Jnum | J:364460 |
| Mgi Id | MGI:8168330 | Doi | 10.1016/j.cmet.2025.01.024 |
| Citation | Sprenger HG, et al. (2025) Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. Cell Metab 37(4):857-869.e9 |
| abstractText | Ergothioneine (EGT) is a diet-derived, atypical amino acid that accumulates to high levels in human tissues. Reduced EGT levels have been linked to age-related disorders, including neurodegenerative and cardiovascular diseases, while EGT supplementation is protective in a broad range of disease and aging models. Despite these promising data, the direct and physiologically relevant molecular target of EGT has remained elusive. Here, we use a systematic approach to identify how mitochondria remodel their metabolome in response to exercise training. From these data, we find that EGT accumulates in muscle mitochondria upon exercise training. Proteome-wide thermal stability studies identify 3-mercaptopyruvate sulfurtransferase (MPST) as a direct molecular target of EGT; EGT binds to and activates MPST, thereby boosting mitochondrial respiration and exercise training performance in mice. Together, these data identify the first physiologically relevant EGT target and establish the EGT-MPST axis as a molecular mechanism for regulating mitochondrial function and exercise performance. |
