ArticleMolecular pharmacology2024
Role of Mitochondrial and Cytosolic Folylpolyglutamate Synthetase in One-Carbon Metabolism and Antitumor Efficacy of Mitochondrial-Targeted Antifolates.
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Article in Molecular pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6citing papers in PubMed
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6 citing papers in PubMed.
- Tissue-Specific Transcriptomic Profiling of Vitamin-Dependent Mitochondrial Pathways in Female Buffalo.Cell biochemistry and biophysics · 2026Article
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Multifaceted role of serine hydroxymethyltransferase in health and disease.Molecules and cells · 2025Review
- Pharmacodynamic determinants of mitochondrial one-carbon flux and serine hydroxymethyltransferase inhibition in human tumors.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Structural Characterization of 5-Substituted Pyrrolo[3,2-Biochemistry · 2024Article
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Authors and funding
14 authors.
Carrie O'ConnorDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.).
Mathew SchneiderDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.).
Jade M KatinasDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.).
Md Junayed NayeenDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.).
Khushbu ShahDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.).
Tejashree MagdumDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.).
Abhishekh SharmaDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.).
Seongho KimDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.).
Xun BaoDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.).
Jing LiDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.).
Charles E DannDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.).
Aleem GangjeeDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.).
Larry H MatherlyDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.) houz@karmanos.org matherly@karmanos.org.
Zhanjun HouDepartment of Oncology (C.O., M.S., S.K., X.B., J.L., L.H.M., Z.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., T.M., A.S., A.G.); Department of Chemistry, Indiana University, Bloomington, Indiana (J.M.K., C.E.D.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (S.K., X.B., J.L., L.H.M., Z.H.) houz@karmanos.org matherly@karmanos.org.ORCID 0000-0001-5631-5202
Funding
Tumor Biology and Microenvironment (Program 1)P30CA022453 · NCI · WAYNE STATE UNIVERSITY · PI PAUL M STEMMER · 1985 to 2026
$68.4MMOLECULAR REGULATION OF FOLATE AND ANTIFOLATE TRANSPORTR01CA053535 · NCI · WAYNE STATE UNIVERSITY · PI HOU, ZHANJUN, MATHERLY, LARRY H · 1993 to 2024
$6.3MTRAINING PROGRAM IN THE BIOLOGY OF CANCERT32CA009531 · NCI · WAYNE STATE UNIVERSITY · PI Larry H Matherly · 1985 to 2026
$5.3MTherapeutic Targeting Mitochondrial C1 MetabolismR01CA250469 · NCI · WAYNE STATE UNIVERSITY · PI DANN, CHARLES E., GANGJEE, ALEEM · 2021 to 2025
$3.0MNCI NIH HHS P30 CA022453NCI NIH HHS R01 CA053535NCI NIH HHS R01 CA250469NCI NIH HHS T32 CA009531
Abstract
Folate-dependent one-carbon (C1) metabolism encompasses distinct cytosolic and mitochondrial pathways connected by an interchange among serine, glycine, and formate. In both the cytosol and mitochondria, folates exist as polyglutamates, with polyglutamylation catalyzed by folylpolyglutamate synthetase (FPGS), including cytosolic and mitochondrial isoforms. Serine is metabolized by serine hydroxymethyltransferase (SHMT)2 in the mitochondria and generates glycine and C1 units for cellular biosynthesis in the cytosol.
Indexed as
CytosolFolic Acid AntagonistsMitochondriaPeptide SynthasesAntineoplastic AgentsCarbonCell Line, TumorFolic AcidGlycine HydroxymethyltransferaseHumansPancreatic NeoplasmsAntineoplastic AgentsCarbonFolic AcidFolic Acid Antagonistsfolylpolyglutamate synthetaseGlycine HydroxymethyltransferasePeptide SynthasesSHMT protein, human
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