Functional interplay among thiol-based redox signaling, metabolism, and ferroptosis unveiled by a genetic variant of TP53
Open accessAbstract
Significance: Thiol-mediated protein cysteine modifications represent important, but often overlooked, physiologic regulatory determinants. We previously reported that the codon 47 variants of TP53 associate with differences in the intracellular abundance of low molecular weight (LMW) thiol metabolites, directly promoting enhanced resistance to the oxidative death process of ferroptosis in S47 cells. We now report that these polymorphic variants also associate with distinct metabolic profiles, including the redox-mediated, reversible reprogramming of glycolytic metabolism. The observed metabolic differences are mechanistically linked to changes in the activities of key physiologic regulatory proteins, including ATF4, GAPDH, and G6PD. The results support LMW thiol abundance as a critical factor in the regulation of adaptive, coordinated, metabolic signaling networks and oxidative stress response pathways.
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Depletion of CoA contributes to the induction of ferroptosis by erastin.
“Reflecting on recent reports suggesting that depletion of CoA contributes to the induction of ferroptosis by erastin (25, 26)”
From Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction (2022) · cites this paper as [26]
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Fueling Death: The Metabolic Control of Ferroptosis
Carrà, G., Scalera, A., Barbieri, I., Menga, A., & Porporato, P. E. (2026) · Advances in experimental medicine and biology · doi:10.1007/978-3-032-12166-0_16
- Authors
- Leu, J. I.-J., Murphy, M. E., & George, D. L.
- Affiliations
- University of Pennsylvania (US)
- The Wistar Institute (US)
- Corresponding author
- Murphy, Maureen E.
- George, Donna L.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2020-10-14
- Volume
- 117
- Issue
- 43
- Pages
- 26804-26811
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC7604449
- OpenAlex
- W3092668098
- Cited by
- 47
- References
- 60
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 12 · 2023: 7 · 2022: 11 · 2021: 9
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Cancer Institute (P01 CA114046, R01 CA139319, R01 CA102184)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- low molecular weight thiols, glutathione, coenzyme A, redox signaling, ferroptosis, ATF4, metabolic reprogramming, pentose phosphate pathway, glycolysis, NADPH, oxidative stress, glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphate dehydrogenase, African descent populations
- MeSH terms
- Ferroptosis, Animals, Cell Line, Coenzyme A, Glutathione, Glycolysis, Homeostasis, Humans, Male, Oxidation-Reduction, Protein Processing, Post-Translational, Sulfhydryl Compounds, Genes, p53, Mice, Activating Transcription Factor 4
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