ArticleThe Journal of biological chemistry2010
Mitochondrial C1-tetrahydrofolate synthase (MTHFD1L) supports the flow of mitochondrial one-carbon units into the methyl cycle in embryos.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 113 citations in OpenAlex.
- Relationship between folate concentration and expression of folate-associated genes in tissue and plasma after intraoperative administration of leucovorin in patients with colorectal cancer.Cancer chemotherapy and pharmacology · 2018Trial
- Hypoxia-driven microRNA-27b underlies pathologic cardiac endoreplication in heart disease.Signal transduction and targeted therapy · 2026Article
- Dual-stress-responsive-pathways prevent HCC initiation via p53 suppression of MTHFD1L-RNA mResearch square · 2026Article
- MTHFD1L in muscle invasive bladder cancer: a multi-cohort study on prognosis and therapeutic response.World journal of surgical oncology · 2026Article
- MTHFD2: A Retrospective and a Glance into the Future.International journal of molecular sciences · 2025Review
- Characterization of an Activated Metabolic Transcriptional Program in Hepatoblastoma Tumor Cells Using scRNA-seq.International journal of molecular sciences · 2024Article
- Mitochondrial One-Carbon Metabolism and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Optical coherence tomography-guided Brillouin microscopy highlights regional tissue stiffness differences during anterior neural tube closure in the Mthfd1l murine mutant.Development (Cambridge, England) · 2024Article
- Structural Characterization of 5-Substituted Pyrrolo[3,2-Biochemistry · 2024Article
- Identifying the role of MTHFD1L in prostate cancer progression from genetic analysis and experimental validation.American journal of cancer research · 2024Article
- The negative effect of G1958A polymorphism on MTHFD1 protein stability and HCC growth.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Article
- The First Structure of Human MTHFD2L and Its Implications for the Development of Isoform-Selective Inhibitors.ChemMedChem · 2022Article
- The catalytic mechanism of the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2).PLoS computational biology · 2022Article
- Serine and one-carbon metabolisms bring new therapeutic venues in prostate cancer.Discover oncology · 2021Review
- Hormonal regulation of glycine decarboxylase and its relationship to oxidative stress.Physiological reports · 2021Article
- Evidence for the Role of Mitochondrial DNA Release in the Inflammatory Response in Neurological Disorders.International journal of molecular sciences · 2021Review
- Metabotype analysis of Mthfd1l-null mouse embryos using desorption electrospray ionization mass spectrometry imaging.Analytical and bioanalytical chemistry · 2021Article
- Article
- NAD-dependent methylenetetrahydrofolate dehydrogenase inhibits oral squamous cell carcinoma cell proliferation and promotes apoptosis.Translational cancer research · 2021Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
Mitochondrial folate-dependent one-carbon (1-C) metabolism converts 1-C donors such as serine and glycine to formate, which is exported and incorporated into the cytoplasmic tetrahydrofolate (THF) 1-C pool. Developing embryos depend on this mitochondrial pathway to provide 1-C units for cytoplasmic process such as de novo purine biosynthesis and the methyl cycle. This pathway is composed of sequential methylene-THF dehydrogenase, methenyl-THF cyclohydrolase, and 10-formyl-THF synthetase activities. In embryonic mitochondria, the bifunctional MTHFD2 enzyme catalyzes the dehydrogenase and cyclohydrolase reactions, but the enzyme responsible for the mitochondrial synthetase reaction has not been identified in embryos. A monofunctional 10-formyl-THF synthetase (MTHFD1L gene product) functions in adult mitochondria and is a likely candidate for the embryonic activity. Here we show that the MTHFD1L enzyme is present in mitochondria from normal embryonic tissues and embryonic fibroblast cell lines, and embryonic mitochondria possess the ability to synthesize formate from glycine. The MTHFD1L transcript was detected at all stages of mouse embryogenesis examined. In situ hybridizations showed that MTHFD1L was expressed ubiquitously throughout the embryo but with localized regions of higher expression. The spatial pattern of MTHFD1L expression was virtually indistinguishable from that of MTHFD2 and MTHFD1 (cytoplasmic C(1)-THF synthase) in embryonic day 9.5 mouse embryos, suggesting coordinated regulation. Finally, we show using stable isotope labeling that in an embryonic mouse cell line, greater than 75% of 1-C units entering the cytoplasmic methyl cycle are mitochondrially derived. Thus, a complete pathway of enzymes for supplying 1-C units from the mitochondria to the methyl cycle in embryonic tissues is established.
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