Cited by 50Redox biology and oxidative stressGenomics, phytochemicals, and oxidative stressFerroptosis and cancer prognosis

Functional interplay among thiol-based redox signaling, metabolism, and ferroptosis unveiled by a genetic variant of TP53

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Leu, Julia I-Ju, Murphy, Maureen E., George, Donna L.·2020·Proceedings of the National Academy of Sciences

Abstract

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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Crossref · 10.1073/pnas.2009943117

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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
Published
2020-10-14
Volume
117
Issue
43
Pages
26804-26811
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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