ArticleMolecular cell2018
Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs.
Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.
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Who cites it
132 citing papers in PubMed, 208 citations in OpenAlex.
- Covalent Inhibition of SHMT2 by Gambogic Acid Induces Ferroptosis Through Mitochondrial Collapse in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Glycine as a Metabolic Regulator of Reproductive Function in Livestock: From Gametes to Early Embryos.Animals : an open access journal from MDPI · 2026Review
- The aberration of key amino acids participated one-carbon metabolism may jeopardize genetic stability in cancer development.Cell communication and signaling : CCS · 2026Review
- Review
- SHMT2 deficiency disrupts transcriptional regulation through homocysteine-mediated suppression of histone lactylation in Huntington's disease models.The Journal of clinical investigation · 2026Article
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- SLC6A6 imports taurine into mitochondria to sustain mitochondrial translation and tumour growth.Nature metabolism · 2026Article
- Building a credibility-based framework for target discovery: Perspectives from tRNA synthetase-linked metabolic diseases.Briefings in bioinformatics · 2026Article
- Targeting one-carbon metabolic vulnerabilities of metastasis with therapeutic potential.bioRxiv : the preprint server for biology · 2026Article
- Associations Between Right Ventricular Remodeling, Exercise and Circulating Metabolites in Volume and Pressure Overload States.JACC. Asia · 2026Article
- Hypoxia facilitates triple-negative breast cancer stem cells enrichment and stemness maintenance through oxidized ataxia telangiectasia mutated-induced one-carbon metabolism.World journal of stem cells · 2026Article
- A Nonketotic Hyperglycinemia Mouse Shows Wide-Ranging Biochemical Consequences of Elevated Glycine, Reduced Folate One-Carbon Charging, and Serine Deficiency.Journal of inherited metabolic disease · 2026Article
- Research on serine hydroxymethyltransferase 2 mechanisms in malignant tumor development and progression.PeerJ · 2026Review
- One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.Cancer metastasis reviews · 2025Review
- Non-canonical dihydrolipoyl transacetylase promotes chemotherapy resistance via mitochondrial tetrahydrofolate signaling.Nature communications · 2025Article
- Multifaceted role of serine hydroxymethyltransferase in health and disease.Molecules and cells · 2025Review
- RNA-mediated inhibition of mitochondrial SHMT2 impairs cancer cell proliferation.Cell death discovery · 2025Article
- One-Carbon Metabolism Inhibition Depletes Purines and Results in Profound and Prolonged Ewing Sarcoma Growth Suppression.Cancer research communications · 2025Article
- SHMT2 overexpression improves glaucoma by enhancing mitophagy in retinal ganglion cells through promoting the phospho of PINK1.Diagnostic pathology · 2025Article
- Caloric restriction mimetic 2-deoxyglucose alters metabolic and transcriptomic phenotype in association with changes in chromatin accessibility in human astrocytes.Scientific reports · 2025Article
72 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Upon glucose restriction, eukaryotic cells upregulate oxidative metabolism to maintain homeostasis. Using genetic screens, we find that the mitochondrial serine hydroxymethyltransferase (SHMT2) is required for robust mitochondrial oxygen consumption and low glucose proliferation. SHMT2 catalyzes the first step in mitochondrial one-carbon metabolism, which, particularly in proliferating cells, produces tetrahydrofolate (THF)-conjugated one-carbon units used in cytoplasmic reactions despite the presence of a parallel cytoplasmic pathway. Impairing cytoplasmic one-carbon metabolism or blocking efflux of one-carbon units from mitochondria does not phenocopy SHMT2 loss, indicating that a mitochondrial THF cofactor is responsible for the observed phenotype. The enzyme MTFMT utilizes one such cofactor, 10-formyl THF, producing formylmethionyl-tRNAs, specialized initiator tRNAs necessary for proper translation of mitochondrially encoded proteins. Accordingly, SHMT2 null cells specifically fail to maintain formylmethionyl-tRNA pools and mitochondrially encoded proteins, phenotypes similar to those observed in MTFMT-deficient patients. These findings provide a rationale for maintaining a compartmentalized one-carbon pathway in mitochondria.
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