ArticleCell metabolism2016
Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway.
Article in Cell metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 240 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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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
240 citing papers in PubMed, 1 synthesis or guideline pooled it, 430 citations in OpenAlex.
- Advances in highly active one-carbon metabolism in cancer diagnosis, treatment and drug resistance: A systematic review.Frontiers in oncology · 2022Pooled it
- One-Carbon Metabolism and Midbrain Dopaminergic Cells in Lesch-Nyhan Disease.Molecular syndromology · 2026Review
- Mitochondrial depolarization stabilizes the vitamin BProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Regional HNSCC metabolomics reveals widespread changes to one-carbon metabolism and S-adenosylmethionine metabolism across tumour core, tumour edge and adjacent non-tumour tissues.British journal of cancer · 2026Article
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Tumoral Metabolism at the Intersection of Oncogene Signaling, Epigenetics and Immunology: Emerging Therapeutic Strategies in Cancer.Current issues in molecular biology · 2026Review
- The aberration of key amino acids participated one-carbon metabolism may jeopardize genetic stability in cancer development.Cell communication and signaling : CCS · 2026Review
- A Stable Isotope Tracing Primer for the Mass Spectrometrist.Annual review of analytical chemistry (Palo Alto, Calif.) · 2026Review
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- ALDH1L2 regulates reactive oxygen species and acinar-to-ductal metaplasia in the pancreas.Nature metabolism · 2026Article
- Mitochondria-transliterated ALDH1L1 functions as a feedback regulator of redox homeostasis in cancer cells to enhance the resistance to pro-oxidative therapy.Cell death and differentiation · 2026Article
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- Mitochondrial uncoupling inhibits serine catabolismCancer biology & medicine · 2026Article
- Photorespiration is linked to DNA methylation by formate as a one-carbon source.Nature plants · 2026Article
- Folic Acid Metabolism and Its Impact on Neurogenesis: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2026Review
- Mitochondrial formate dehydrogenase links mitochondrial and cytosolic one carbon metabolism via a one-carbon shunt.Plant physiology · 2026Review
- Research on serine hydroxymethyltransferase 2 mechanisms in malignant tumor development and progression.PeerJ · 2026Review
- Glycine promotes cardiomyocyte proliferation and heart regeneration via the GCN2/AKT signaling axis.Theranostics · 2026Article
- Mitochondrial depolarization stabilizes the vitamin B12 chaperone MMADHC in the cytosol to increase MTR activity.bioRxiv : the preprint server for biology · 2025Article
- Article
180 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
One-carbon (1C) units for purine and thymidine synthesis can be generated from serine by cytosolic or mitochondrial folate metabolism. The mitochondrial 1C pathway is consistently overexpressed in cancer. Here, we show that most but not all proliferating mammalian cell lines use the mitochondrial pathway as the default for making 1C units. Clustered regularly interspaced short palindromic repeats (CRISPR)-mediated mitochondrial pathway knockout activates cytosolic 1C-unit production. This reversal in cytosolic flux is triggered by depletion of a single metabolite, 10-formyl-tetrahydrofolate (10-formyl-THF), and enables rapid cell growth in nutrient-replete conditions. Loss of the mitochondrial pathway, however, renders cells dependent on extracellular serine to make 1C units and on extracellular glycine to make glutathione. HCT-116 colon cancer xenografts lacking mitochondrial 1C pathway activity generate the 1C units required for growth by cytosolic serine catabolism. Loss of both pathways precludes xenograft formation. Thus, either mitochondrial or cytosolic 1C metabolism can support tumorigenesis, with the mitochondrial pathway required in nutrient-poor conditions.
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What 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.