ArticleCell2018
Mitochondrial One-Carbon Pathway Supports Cytosolic Folate Integrity in Cancer Cells.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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
64 citing papers in PubMed, 108 citations in OpenAlex.
- Excess folate elevates formaldehyde genotoxicity in cell lines but not in mice or humans.EMBO molecular medicine · 2026Article
- Review
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- Mitochondrial formate dehydrogenase links mitochondrial and cytosolic one carbon metabolism via a one-carbon shunt.Plant physiology · 2026Review
- A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis.Science (New York, N.Y.) · 2025Article
- Metabolites in the extracellular tumor microenvironment and the shaping of macrophage function.Molecular cell · 2025Review
- Upregulation ofIndian journal of clinical biochemistry : IJCB · 2025Article
- Inhibition of NAD-GPx4 axis and MEK triggers ferroptosis to suppress pancreatic ductal adenocarcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- NAD kinase essentiality in cancer: in real life, it is all about folates.Nature metabolism · 2025Article
- The Role of Mitochondrial Solute Carriers SLC25 in Cancer Metabolic Reprogramming: Current Insights and Future Perspectives.International journal of molecular sciences · 2024Review
- Conditional lethality profiling reveals anticancer mechanisms of action and drug-nutrient interactions.Science advances · 2024Article
- Homeostatic regulation of NAD(H) and NADP(H) in cells.Genes & diseases · 2024Review
- PHGDH: a novel therapeutic target in cancer.Experimental & molecular medicine · 2024Review
- CYP3A5 unexpectedly regulates glucose metabolism through the AKT-TXNIP-GLUT1 axis in pancreatic cancer.Genes & diseases · 2024Article
- Cycling back to folate metabolism in cancer.Nature cancer · 2024Review
- Small molecule mediators of host-T. cruzi-environment interactions in Chagas disease.PLoS pathogens · 2024Review
- Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses.Nature communications · 2024Article
- A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance.Life science alliance · 2023Article
- Phylogenetic Analysis Guides Transporter Protein Deorphanization: A Case Study of the SLC25 Family of Mitochondrial Metabolite Transporters.Biomolecules · 2023Article
4 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
13 authors at 3 institutions in 1 country.
Funding
Abstract
Mammalian folate metabolism is comprised of cytosolic and mitochondrial pathways with nearly identical core reactions, yet the functional advantages of such an organization are not well understood. Using genome-editing and biochemical approaches, we find that ablating folate metabolism in the mitochondria of mammalian cell lines results in folate degradation in the cytosol. Mechanistically, we show that QDPR, an enzyme in tetrahydrobiopterin metabolism, moonlights to repair oxidative damage to tetrahydrofolate (THF). This repair capacity is overwhelmed when cytosolic THF hyperaccumulates in the absence of mitochondrially produced formate, leading to THF degradation. Unexpectedly, we also find that the classic antifolate methotrexate, by inhibiting its well-known target DHFR, causes even more extensive folate degradation in nearly all tested cancer cell lines. These findings shed light on design features of folate metabolism, provide a biochemical basis for clinically observed folate deficiency in QDPR-deficient patients, and reveal a hitherto unknown and unexplored cellular effect of methotrexate.
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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.