Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
PubMed
39965563
DOI
10.1016/j.cmet.2025.01.024
PII: S1550-4131(25)00024-5
Knihovny.cz E-zdroje
- Klíčová slova
- MPST, ergothioneine, exercise, mitochondria,
- MeSH
- ergothionein * metabolismus farmakologie MeSH
- kondiční příprava zvířat * MeSH
- lidé MeSH
- mitochondrie * metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- sulfurtransferasy * metabolismus MeSH
- svalové mitochondrie * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ergothionein * MeSH
- sulfurtransferasy * MeSH
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.
Department of Cancer Biology Dana Farber Cancer Institute Boston MA USA
Department of Cell Biology Harvard Medical School Boston MA USA
Institute of Organic Chemistry and Biochemistry Prague Czech Republic
Whitehead Institute for Biomedical Research Cambridge MA USA
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