The unusual amino acid L-ergothioneine is a physiologic cytoprotectant
Open accessAbstract
Ergothioneine (ET) is an unusual sulfur-containing derivative of the amino acid, histidine, which is derived exclusively through the diet. Although ET was isolated a century ago, its physiologic function has not been clearly established. Recently, a highly specific transporter for ET (ETT) was identified in mammalian tissues, which explains abundant tissue levels of ET and implies a physiologic role. Using RNA interference, we depleted cells of its transporter. Cells lacking ETT are more susceptible to oxidative stress, resulting in increased mitochondrial DNA damage, protein oxidation and lipid peroxidation. ETT is concentrated in mitochondria, suggesting a specific role in protecting mitochondrial components such as DNA from oxidative damage associated with mitochondrial generation of superoxide. In combating cytotoxic effects of pyrogallol, a known superoxide generator, ET is as potent as glutathione. Because of its dietary origin and the toxicity associated with its depletion, ET may represent a new vitamin whose physiologic roles include antioxidant cytoprotection.
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Tissue levels of ERG depend on exogenous supply and are well correlated with expression levels of SLC22A4.
“Tissue levels of ERG depend on an exogenous supply(179), but are then well correlated with the expression levels of SLC22A4(3,180).”
From The biology of ergothioneine, an antioxidant nutraceutical (2020) · cites this paper as [3]
Studies of the effects of ERG have in general been rather descriptive in nature and at the level of processes rather than mechanisms.
“studies of the effects of ERG have in general(449) been rather descriptive in nature. Many have been at the level of processes rather than mechanisms”
From The biology of ergothioneine, an antioxidant nutraceutical (2020) · cites this paper as [3]
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The biology of ergothioneine, an antioxidant nutraceutical
Borodina, I., Kenny, L. C., McCarthy, C. M., Paramasivan, K., Pretorius, E., Roberts, T. J., van der Hoek, S. A., & Kell, D. B. (2020) · Nutrition Research Reviews · doi:10.1017/s0954422419000301 · Cited by 296 · see citing works
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- Authors
- Paul, B. D., & Snyder, S. H.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Snyder, S H
- ORCID
- Venue
- Cell Death & Differentiation
- Published
- 2009-11-13
- Volume
- 17
- Issue
- 7
- Pages
- 1134-1140
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- PMC
- PMC2885499
- OpenAlex
- W1989971736
- Cited by
- 304
- References
- 3
- Citations by year
- 2026: 33 · 2025: 31 · 2024: 24 · 2023: 28 · 2022: 25 · 2021: 28 · 2020: 13 · 2019: 16 · 2018: 13 · 2017: 15 · 2016: 13 · 2015: 13 · 2014: 16 · 2013: 9 · 2012: 10
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (P50DA000266, DA 00074, DA.00266, K05DA000074)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- ergothioneine, cytoprotection, oxidative stress, mitochondrial DNA damage, superoxide, lipid peroxidation, protein oxidation, glutathione, sulfur-containing amino acids, dietary amino acids, mitochondrial targeting
- MeSH terms
- Antioxidants, DNA Damage, Ergothioneine, HeLa Cells, Humans, Mitochondria, Lipid Peroxidation, Reactive Oxygen Species, Oxidative Stress, Cytoprotection, Organic Cation Transport Proteins, Symporters, RNA Interference
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