ArticleActa naturae2014
The Role of Dihydroorotate Dehydrogenase in Apoptosis Induction in Response to Inhibition of the Mitochondrial Respiratory Chain Complex III.
Article in Acta naturae, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Pathological Changes in Liver Mitochondria of Rats with Experimentally Induced Hyperthyroidism and Their Correction with Uridine.Cell biochemistry and biophysics · 2025Article
- De novo pyrimidine biosynthesis inhibition synergizes with BCL-XNature communications · 2025Article
- Mechanisms of S-phase arrest and mitochondrial dysfunction in complex III by DHODH inhibitors in tumorigenic TNBC cells.Histochemistry and cell biology · 2024Article
- Drug repurposing for cancer therapy.Signal transduction and targeted therapy · 2024Review
- The Warburg effect modulates DHODH role in ferroptosis: a review.Cell communication and signaling : CCS · 2023Review
- LY294002 alleviates bone cancer pain by reducing mitochondrial dysfunction and the inflammatory response.International journal of molecular medicine · 2023Article
- Caffeic Acid Phenethyl Ester as a DHODH Inhibitor and Its Synergistic Anticancer Properties in Combination with 5-Fluorouracil in a Breast Cancer Cell Line.Journal of experimental pharmacology · 2022Article
- DHODH and cancer: promising prospects to be explored.Cancer & metabolism · 2021Review
- The Role of Pi, Glutamine and the Essential Amino Acids in Modulating the Metabolism in Diabetes and Cancer.Journal of diabetes and metabolic disorders · 2020Review
- Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria.eLife · 2020Article
- Teriflunomide preserves peripheral nerve mitochondria from oxidative stress-mediated alterations.Therapeutic advances in chronic disease · 2020Article
- Direct and Indirect Targeting of HOXA9 Transcription Factor in Acute Myeloid Leukemia.Cancers · 2019Review
- Novel AR-12 derivatives, P12-23 and P12-34, inhibit flavivirus replication by blocking host de novo pyrimidine biosynthesis.Emerging microbes & infections · 2018Article
- Implication of KRT16, FAM129A and HKDC1 genes as ATF4 regulated components of the integrated stress response.PloS one · 2018Article
- Effects of microgravity on osteoblast mitochondria: a proteomic and metabolomics profile.Scientific reports · 2017Article
- Checkpoint kinase 1 inhibition sensitises transformed cells to dihydroorotate dehydrogenase inhibition.Oncotarget · 2017Article
- Mitochondrial dysfunction induces SESN2 gene expression through Activating Transcription Factor 4.Cell cycle (Georgetown, Tex.) · 2016Article
- Magnetic field effects as a result of the radical pair mechanism are unlikely in redox enzymes.Journal of the Royal Society, Interface · 2015Article
- Mouse Models of Rare Craniofacial Disorders.Current topics in developmental biology · 2015Review
- A sustained deficiency of mitochondrial respiratory complex III induces an apoptotic cell death through the p53-mediated inhibition of pro-survival activities of the activating transcription factor 4.Cell death & disease · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A mechanism for the induction of programmed cell death (apoptosis) upon dysfunction of the mitochondrial respiratory chain has been studied. Previously, we had found that inhibition of mitochondrial cytochrome bc1, a component of the electron transport chain complex III, leads to activation of tumor suppressor p53, followed by apoptosis induction. The mitochondrial respiratory chain is coupled to the de novo pyrimidine biosynthesis pathway via the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). The p53 activation induced in response to the inhibition of the electron transport chain complex III has been shown to be triggered by the impairment of the de novo pyrimidine biosynthesis due to the suppression of DHODH. However, it remained unclear whether the suppression of the DHODH function is the main cause of the observed apoptotic cell death. Here, we show that apoptosis in human colon carcinoma cells induced by the mitochondrial respiratory chain complex III inhibition can be prevented by supplementation with uridine or orotate (products of the reaction catalyzed by DHODH) rather than with dihydroorotate (a DHODH substrate). We conclude that apoptosis is induced in response to the impairment of the de novo pyrimidine biosynthesis caused by the inhibition of DHODH. The conclusion is supported by the experiment showing that downregulation of DHODH by RNA interference leads to accumulation of the p53 tumor suppressor and to apoptotic cell death.
Indexed as
Identifiers
24772329PMC3999468W2136718794What OpenQuestion holds
Registered trials
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.