MTHFD2L

Last update 08 May 2025

Basic Info

Synonyms

Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial, Methenyltetrahydrofolate cyclohydrolase, methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 like

+ [5]

Introduction

Bifunctional mitochondrial folate-interconverting enzyme that has both NAD/NADP-dependent methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities.

100 Clinical Results associated with MTHFD2L

100 Translational Medicine associated with MTHFD2L

0 Patents (Medical) associated with MTHFD2L

Literatures (Medical) associated with MTHFD2L

01 Aug 2025·The International Journal of Biochemistry & Cell Biology

CAPRIN1/TYMS/MTHFD2 axis promotes EMT process in nasopharyngeal carcinoma development

Article

Author: Sun, Guihu ; Li, Dawei ; Cao, Hongwei ; Wang, Kunrong ; Yan, Aihui ; Guo, Shuang ; Yu, Hanbing ; Xing, Dongsheng

BACKGROUNDNasopharyngeal carcinoma (NPC) is a type of malignant tumor occurring in the nasopharynx. It frequently leads to treatment failure after metastasis, often resulting from epithelial-mesenchymal transition (EMT). Thymidylate synthetase (TYMS) is a key enzyme involved in DNA synthesis and replication. Currently, the role of TYMS and its mechanism of upstream and downstream in EMT of NPC is unclear.METHODSNPC cell lines HK-1 and C666-1 were used in this study. Lentivirus carrying TYMS knockdown and overexpressed plasmids were used to regulate TYMS expression. Cell migration and invasion were examined using the wound-healing and Transwell assays, respectively. C666-1 cells were injected into the axilla and tail vein of mice to form subcutaneous tumors and construct lung metastasis model, respectively. RNA immunoprecipitation assay was used to examine the interaction between protein and mRNA. RNA-seq was performed to explore the downstream regulatory mechanism of TYMS.RESULTSTYMS was highly expressed in NPC tissues. TYMS silencing and upregulation inhibited and promoted EMT processes in NPC cells, respectively, as demonstrated by the expression of EMT-related proteins, including E-cadherin, Slug, MMP2, and MMP9. Cytoplasmic activation/proliferation-associated protein-1 (CAPRIN1), a protein bound with TYMS mRNA, promoted the EMT process in NPC cells. Meanwhile, TYMS knockdown reversed the effect of CAPRIN1 overexpression. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) was down-regulated following TYMS silencing. MTHFD2 knockdown abolished the effect of TYMS overexpression.CONCLUSIONCAPRIN1/TYMS/MTHFD2 axis drives the EMT process and thus promotes NPC development, which is a promising target in therapy and adjuvant therapy of NPC.

01 Mar 2025·Nature Chemical Biology

Metabolic determinants of germinal center B cell formation and responses

Article

Author: Xiang, Chen ; Zhou, Jiawen ; Li, Gen ; Jiang, Peng ; Wu, Jun ; Chen, Haiyan ; Sun, Xuan

Germinal center (GC) B cells are crucial for the generation of GCs and long-lived humoral immunity. Here we report that one-carbon metabolism determines the formation and responses of GC B cells. Upon CD40 stimulation, GC B cells selectively upregulate methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) expression to generate purines and the antioxidant glutathione. MTHFD2 depletion reduces GC B cell frequency and antigen-specific antibody production. Moreover, supplementation with nucleotides and antioxidants suffices to promote GC B cell formation and function in vitro and in vivo through activation of the mammalian target of rapamycin complex 1 signaling pathway. Moreover, we found that antigen stimulation enhances YY1 binding to the Mthfd2 promoter and promotes MTHFD2 transcription. Interestingly, these findings can be generalized to the pentose phosphate pathway, which is another major source of reducing power and nucleotides. Therefore, these results suggest that an increased capacity for nucleotide synthesis and redox balance is required for GC B cell formation and responses, revealing a key aspect of GC B cell fate determination.

31 Dec 2024·Renal Failure

EP300-mediated H3 acetylation elevates MTHFD2 expression to reduce mitochondrial dysfunction in lipopolysaccharide-induced tubular epithelial cells

Article

Author: Hu, Weike

Sepsis represents an organ dysfunction resulting from the host's maladjusted response to infection, and can give rise to acute kidney injury (AKI), which significantly increase the morbidity and mortality of septic patients. This study strived for identifying a novel therapeutic strategy for patients with sepsis-induced AKI (SI-AKI). Rat tubular epithelial NRK-52E cells were subjected to lipopolysaccharide (LPS) exposure for induction of in-vitro SI-AKI. The expressions of E1A binding protein p300 (EP300) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) in NRK-52E cells were assessed by western blot and qRT-PCR, and their interaction was explored by chromatin immunoprecipitation performed with antibody for H3K27 acetylation (H3K27ac). The effect of them on SI-AKI-associated mitochondrial dysfunction of tubular epithelial cells was investigated using transfection, MTT assay, TUNEL staining, 2',7'-Dichlorodihydrofluorescein diacetate probe assay, Mitosox assay, and JC-1 staining. MTHFD2 and EP300 were upregulated by LPS exposure in NRK-52E cells. LPS increased the acetylation of H3 histone in the MTHFD2 promoter region, and EP300 suppressed the effect of LPS. EP300 ablation inhibited the expression of MTHFD2. MTHFD2 overexpression antagonized LPS-induced viability reduction, apoptosis promotion, reactive oxygen species overproduction, and mitochondrial membrane potential collapse of NRK-52E cells. By contrast, MTHFD2 knockdown and EP300 ablation brought about opposite consequences. Furthermore, MTHFD2 overexpress and EP300 ablation counteracted each other's effect in LPS-exposed NRK-52E cells. EP300-mediated H3 acetylation elevates MTHFD2 expression to reduce mitochondrial dysfunction of tubular epithelial cells in SI-AKI.

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MTHFD2L

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