ArticleBioscience reports2013
Dihydro-orotate dehydrogenase is physically associated with the respiratory complex and its loss leads to mitochondrial dysfunction.
Article in Bioscience reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 137 citations in OpenAlex.
- Metabolic response to extended continuous positive airway pressure in premature infants.Pediatric research · 2026Trial
- Metabolites with a message: impacts on epigenetics and implications for epimetabopathies.EMBO reports · 2026Review
- DH-AUTAC induces ferroptosis in colorectal cancer by targeting DHODH for autophagic degradation through KCTD10-SQSTM1 signaling.Journal of gastroenterology · 2026Article
- Dynamic control of nucleotide metabolism in physiology and disease.Nature cell biology · 2026Review
- DHODH regulates trophoblast fusion via IFITM-reduced plasma membrane fluidity: Implications for hypertensive disorders of pregnancy.iScience · 2026Article
- Dihydroorotate dehydrogenase (DHODH) regulates trophoblast syncytialization through organelle stress-induced cellular senescence.FEBS open bio · 2026Article
- BCOR mutations define a therapeutic vulnerability to DHODH Inhibition in acute myeloid leukemia.Annals of hematology · 2026Article
- Investigating targeted and untargeted approaches to biomarker discovery in fearful, adult dogs.Journal of animal science · 2026Article
- Dihydroorotate Dehydrogenase as a Modulator of Ferroptosis in Myocardial Ischemia-reperfusion Injury.Current molecular medicine · 2026Article
- Highlighting the Therapeutic Potential of an Underexplored Target: Human Dihydroorotate Dehydrogenase in Cancer, Rheumatoid Arthritis and Sclerosis.Current topics in medicinal chemistry · 2026Review
- Cytochrome c oxidase dependent respiration is essential for T cell activation, proliferation and memory formation.Nature communications · 2025Article
- Pathway coessentiality mapping reveals complex II is required for de novo purine biosynthesis in acute myeloid leukaemia.Nature metabolism · 2025Article
- Review
- Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment.Genes & diseases · 2025Review
- NK-A 17E-233I: a novel competitive inhibitor of human dihydroorotate dehydrogenase (DHODH) for cancer therapy.Journal of experimental & clinical cancer research : CR · 2025Article
- Mitochondrial membrane potential and compartmentalized signaling: Calcium, ROS, and beyond.Redox biology · 2025Review
- De novo pyrimidine biosynthesis inhibition synergizes with BCL-XNature communications · 2025Article
- Powering the powerhouse: Mitochondrial NADPH propels oxidative metabolism.Cell chemical biology · 2025Article
- Mitochondria as a Disease-Relevant Organelle in Rheumatoid Arthritis: A Key Breakout in Fight Against the Disease.Biomedicines · 2025Review
- Engineered mitochondria in diseases: mechanisms, strategies, and applications.Signal transduction and targeted therapy · 2025Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Some mutations of the DHODH (dihydro-orotate dehydrogenase) gene lead to postaxial acrofacial dysostosis or Miller syndrome. Only DHODH is localized at mitochondria among enzymes of the de novo pyrimidine biosynthesis pathway. Since the pyrimidine biosynthesis pathway is coupled to the mitochondrial RC (respiratory chain) via DHODH, impairment of DHODH should affect the RC function. To investigate this, we used siRNA (small interfering RNA)-mediated knockdown and observed that DHODH knockdown induced cell growth retardation because of G₂/M cell-cycle arrest, whereas pyrimidine deficiency usually causes G₁/S arrest. Inconsistent with this, the cell retardation was not rescued by exogenous uridine, which should bypass the DHODH reaction for pyrimidine synthesis. DHODH depletion partially inhibited the RC complex III, decreased the mitochondrial membrane potential, and increased the generation of ROS (reactive oxygen species). We observed that DHODH physically interacts with respiratory complexes II and III by IP (immunoprecipitation) and BN (blue native)/SDS/PAGE analysis. Considering that pyrimidine deficiency alone does not induce craniofacial dysmorphism, the DHODH mutations may contribute to the Miller syndrome in part through somehow altered mitochondrial function.
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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.