ArticleCell metabolism2019
Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells.
Open access · bronzeAbstract read
In one paragraph
Article in Cell metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers.
0numbers the graph read from it
0cells of the map it votes in
167citing papers in PubMed
9.1field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
167 citing papers in PubMed, 302 citations in OpenAlex.
- Lysyl oxidase inhibition disrupts mitochondrial homeostasis to create vulnerability to ferroptosis in TNBC.Cell reports. Medicine · 2026Article
- DH-AUTAC induces ferroptosis in colorectal cancer by targeting DHODH for autophagic degradation through KCTD10-SQSTM1 signaling.Journal of gastroenterology · 2026Article
- Plant-derived mitochondria mitigate aging-related neurodegeneration by reprogramming microglial mitochondrial energy metabolism.Translational neurodegeneration · 2026Article
- Mitochondria transfer in glioblastoma.Neuro-oncology · 2026Review
- DHODH inhibition suppresses cutaneous squamous cell carcinoma growth by the induction of differentiation through perturbation of the cellular redox balance.Cell death & disease · 2026Article
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- Tumor-intrinsic metabolic pathways essential for tumorigenesis and resistance to anti-PD1 in oncogenic Kras-driven lung adenocarcinoma.Cancer & metabolism · 2026Article
- Pan-cancer analysis of pyrimidine metabolism reveals signaling pathways connections with chemoresistance role.British journal of cancer · 2026Article
- Mitochondrial Transfer Rescues Respiration to Support De Novo Pyrimidine Biosynthesis and Tumor Progression.Cancer research · 2026Article
- DHODH turns cytosolic, yet cells keep growing.Nature metabolism · 2026Article
- Antimycin A inhibits alpha-herpesvirus replication by disrupting the formation of pyrimidinosomes.Journal of advanced research · 2026Article
- Ectopic expression of cytosolic DHODH uncouples de novo pyrimidine biosynthesis from mitochondrial electron transport.Nature metabolism · 2026Article
- Potential oncogene VPS72 in hepatocellular carcinoma: prognostic and immune infiltration implications.European journal of medical research · 2026Article
- Metabolic Dependency on De Novo Pyrimidine Synthesis Is a Targetable Vulnerability in Platinum-Resistant Ovarian Cancer.Cancer research · 2026Article
- Targeting opportunities presented by the pyrimidine biosynthesis pathway in Mycobacterium tuberculosis: a brief review.Biochemical Society transactions · 2026Review
- Mitochondrial transfer in the tumor microenvironment: a dynamic determinant of cancer plasticity, immune dysfunction, and therapeutic opportunity.Frontiers in immunology · 2026Review
- Cytochrome c oxidase dependent respiration is essential for T cell activation, proliferation and memory formation.Nature communications · 2025Article
- Mitochondria in focus: From structure and function to their role in human diseases. A review.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2025Review
- Review
- Regenerating liver uses ammonia to support de novo pyrimidine synthesis and cell proliferation.Nature communications · 2025Article
107 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
49 authors at 14 institutions in 8 countries.
Martina BajzikovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic; Faculty of Science, Charles University, 128 44 Prague, Czech Republic.
Jaromira KovarovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic. Electronic address: jaromira.kovarova@ibt.cas.cz.
Ana R CoelhoInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC-Biotech, Biocant Park, 3060-197 Cantanhede, Portugal.
Stepana BoukalovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
Sehyun OhCollege of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul 08826, Korea.
Katerina RohlenovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
David SvecInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
Sona HubackovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
Berwini EndayaSchool of Medical Science, Griffith University, Southport, QLD 4222, Australia.
Kristyna JudasovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
Ayenachew Bezawork-GeletaSchool of Medical Science, Griffith University, Southport, QLD 4222, Australia.
Katarina KluckovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
Laurent ChatreDepartment of Developmental and Stem Cell Biology, Institut Pasteur, 75015 Paris, France; CNRS UMR 3738, Team Stability of Nuclear and Mitochondrial DNA, 75015 Paris, France.
Renata ZobalovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
Anna NovakovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
Katerina VanovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
Zuzana EzrovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic; Faculty of Science, Charles University, 128 44 Prague, Czech Republic.
Ghassan J MaghzalVictor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, UNSW Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
Silvia Magalhaes NovaisInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic; Faculty of Science, Charles University, 128 44 Prague, Czech Republic.
Marie OlsinovaFaculty of Science, Charles University, 128 44 Prague, Czech Republic.
Linda KrobovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
Yong Jin AnCollege of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul 08826, Korea.
Eliska DavidovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic; Faculty of Science, Charles University, 128 44 Prague, Czech Republic.
Zuzana NahackaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
Margarita SobolInstitute of Molecular Genetics, Czech Academy of Sciences, 142 20 Prague, Czech Republic.
Teresa Cunha-OliveiraCNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC-Biotech, Biocant Park, 3060-197 Cantanhede, Portugal.
Cristian Sandoval-AcuñaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
Hynek StrnadInstitute of Molecular Genetics, Czech Academy of Sciences, 142 20 Prague, Czech Republic.
Tongchuan ZhangInstitute for Glycomics, Griffith University, Southport, 4222 QLD, Australia.
Thanh HuynhEunice Kennedy Shriver Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Teresa L SerafimCNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC-Biotech, Biocant Park, 3060-197 Cantanhede, Portugal.
Pavel HozakInstitute of Molecular Genetics, Czech Academy of Sciences, 142 20 Prague, Czech Republic.
Vilma A SardaoCNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC-Biotech, Biocant Park, 3060-197 Cantanhede, Portugal.
Werner J H KoopmanDepartment of Biochemistry (286), Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, 6525 Nijmegen, the Netherlands.
Miria RicchettiDepartment of Developmental and Stem Cell Biology, Institut Pasteur, 75015 Paris, France; CNRS UMR 3738, Team Stability of Nuclear and Mitochondrial DNA, 75015 Paris, France.
Paulo J OliveiraCNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC-Biotech, Biocant Park, 3060-197 Cantanhede, Portugal.
Frantisek KolarInstitute of Physiology, Czech Academy of Sciences, 142 20 Prague, Czech Republic.
Mikael KubistaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
Jaroslav TruksaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic.
Katerina Dvorakova-HortovaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic; Faculty of Science, Charles University, 128 44 Prague, Czech Republic.
Karel PacakEunice Kennedy Shriver Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Robert GurlichThird Faculty Hospital, Charles University, Prague, Czech Republic.
Roland StockerVictor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, UNSW Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
Yaoqi ZhouInstitute for Glycomics, Griffith University, Southport, 4222 QLD, Australia.
Michael V BerridgeMalaghan Institute of Medical Research, Wellington 6242, New Zealand.
Sunghyouk ParkCollege of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul 08826, Korea. Electronic address: psh@snu.ac.kr.
Lanfeng DongSchool of Medical Science, Griffith University, Southport, QLD 4222, Australia. Electronic address: l.dong@griffith.edu.au.
Jakub RohlenaInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic. Electronic address: rohlenaj@ibt.cas.cz.
Jiri NeuzilInstitute of Biotechnology, Czech Academy of Sciences, 252 50, Vestec, Prague-West, Czech Republic; School of Medical Science, Griffith University, Southport, QLD 4222, Australia. Electronic address: j.neuzil@griffith.edu.au.
Czech Academy of Sciences · CZGriffith University · AUCharles University · CZCzech Academy of Sciences, Institute of Biotechnology · CZBiocant · PTSeoul National University · KRCzech Academy of Sciences, Institute of Molecular Genetics · CZEunice Kennedy Shriver National Institute of Child Health and Human Development · USInstitut Pasteur · FRUniversity of Coimbra · PTMalaghan Institute of Medical Research · NZRadboud University Medical Center · NLSt Vincent's Clinic · AUUNSW Sydney · AU
Funding
Diagnosis, Pathophysiology And Molecular Biology of Pheochromocytoma and ParagangliomaZIAHD008735 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI PACAK, KAREL · 2009 to 2024
$28.4MIntramural NIH HHS Z99 HD999999
Abstract
Cancer cells without mitochondrial DNA (mtDNA) do not form tumors unless they reconstitute oxidative phosphorylation (OXPHOS) by mitochondria acquired from host stroma. To understand why functional respiration is crucial for tumorigenesis, we used time-resolved analysis of tumor formation by mtDNA-depleted cells and genetic manipulations of OXPHOS. We show that pyrimidine biosynthesis dependent on respiration-linked dihydroorotate dehydrogenase (DHODH) is required to overcome cell-cycle arrest, while mitochondrial ATP generation is dispensable for tumorigenesis. Latent DHODH in mtDNA-deficient cells is fully activated with restoration of complex III/IV activity and coenzyme Q redox-cycling after mitochondrial transfer, or by introduction of an alternative oxidase. Further, deletion of DHODH interferes with tumor formation in cells with fully functional OXPHOS, while disruption of mitochondrial ATP synthase has little effect. Our results show that DHODH-driven pyrimidine biosynthesis is an essential pathway linking respiration to tumorigenesis, pointing to inhibitors of DHODH as potential anti-cancer agents.
Indexed as
AnimalsCell Line, TumorCell RespirationDihydroorotate DehydrogenaseDNA, MitochondrialHumansMiceMice, Inbred BALB CMice, Inbred C57BLMitochondriaNeoplasmsOxidative PhosphorylationOxidoreductases Acting on CH-CH Group DonorsPyrimidinesUbiquinoneDihydroorotate DehydrogenaseDNA, MitochondrialOxidoreductases Acting on CH-CH Group DonorspyrimidinePyrimidinesUbiquinonecancercoenzyme Qdihydroorotate dehydrogenasemitochondriaOXPHOSpyrimidine biosynthesisrespiration
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.