ArticleProceedings of the National Academy of Sciences of the United States of America2010
Pyrimidine biosynthesis links mitochondrial respiration to the p53 pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 162 citations in OpenAlex.
- The p53-Associated Regulation of ATF4 mRNA Expression Involves p21 and p130 in a Stress-Dependent Manner.Cells · 2026Article
- Arginine metabolism supportsmBio · 2026Article
- Sodium butyrate suppresses endometrial cancer cell growth by inhibiting thymidylate synthase and reprogramming pyrimidine metabolism.Genes & nutrition · 2026Article
- Ferroptosis as a therapeutic target in cancer: mechanisms, immune interactions, and emerging strategies.Molecular cancer · 2026Review
- Pan-cancer analysis of pyrimidine metabolism reveals signaling pathways connections with chemoresistance role.British journal of cancer · 2026Article
- Pathway coessentiality mapping reveals complex II is required for de novo purine biosynthesis in acute myeloid leukaemia.Nature metabolism · 2025Article
- p53-mediated regulation of electron transport chain and nucleotide synthesis during Newcastle disease virus infection.Journal of virology · 2025Article
- Arginine Metabolism SupportsbioRxiv : the preprint server for biology · 2025Article
- Insights into the cellular function and mechanism of action of quinone reductase 2 (NQO2).The Biochemical journal · 2025Review
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- Identification of potential biomarkers and pathways involved in high-altitude pulmonary edema using GC-MS and LC-MS metabolomic methods.Scientific reports · 2024Article
- The role of mitochondria in tumor metastasis and advances in mitochondria-targeted cancer therapy.Cancer metastasis reviews · 2024Review
- Mechanisms of S-phase arrest and mitochondrial dysfunction in complex III by DHODH inhibitors in tumorigenic TNBC cells.Histochemistry and cell biology · 2024Article
- Our current understanding of the biological impact of endometrial cancer mtDNA genome mutations and their potential use as a biomarker.Frontiers in oncology · 2024Review
- The Warburg effect modulates DHODH role in ferroptosis: a review.Cell communication and signaling : CCS · 2023Review
- Mitochondrial complex III deficiency drives c-MYC overexpression and illicit cell cycle entry leading to senescence and segmental progeria.Nature communications · 2023Article
- Intrinsic disorder in the open reading frame 2 of hepatitis E virus: a protein with multiple functions beyond viral capsid.Journal, genetic engineering & biotechnology · 2023Article
- Article
- FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration.Life science alliance · 2022Article
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
42 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
While many functions of the p53 tumor suppressor affect mitochondrial processes, the role of altered mitochondrial physiology in a modulation of p53 response remains unclear. As mitochondrial respiration is affected in many pathologic conditions such as hypoxia and intoxications, the impaired electron transport chain could emit additional p53-inducing signals and thereby contribute to tissue damage. Here we show that a shutdown of mitochondrial respiration per se does not trigger p53 response, because inhibitors acting in the proximal and distal segments of the respiratory chain do not activate p53. However, strong p53 response is induced specifically after an inhibition of the mitochondrial cytochrome bc1 (the electron transport chain complex III). The p53 response is triggered by the deficiency in pyrimidines that is developed due to a suppression of the functionally coupled mitochondrial pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH). In epithelial carcinoma cells the activation of p53 in response to mitochondrial electron transport chain complex III inhibitors does not require phosphorylation of p53 at Serine 15 or up-regulation of p14(ARF). Instead, our data suggest a contribution of NQO1 and NQO2 in stabilization of p53 in the nuclei. The results establish the deficiency in pyrimidine biosynthesis as the cause of p53 response in the cells with impaired mitochondrial respiration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.