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Literature summary for 1.5.1.15 extracted from

  • Yue, L.; Pei, Y.; Zhong, L.; Yang, H.; Wang, Y.; Zhang, W.; Chen, N.; Zhu, Q.; Gao, J.; Zhi, M.; Wen, B.; Zhang, S.; Xiang, J.; Wei, Q.; Liang, H.; Cao, S.; Lou, H.; Chen, Z.; Han, J.
    Mthfd2 modulates mitochondrial function and DNA repair to maintain the pluripotency of mouse stem cells (2020), Stem Cell Reports, 15, 529-545 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.5.1.15

Protein Variants

Protein Variants Comment Organism
additional information short hairpin RNAs (shRNAs) suppression of expression of Mthfd2 gene in E14 mouse embryonic stem cells (mESCs). Mthfd2 knockdown (KD) results in loss of typical stem cell morphology, with reduced alkaline phosphatase (AP) staining. The expression of pluripotency marker genes is downregulated and that of lineage marker genes upregulated, showing that Mthfd2 depletion results in differentiation of mESCs. Knockdown of Mthfd2 in another G4 mESC line shows results consistent with those in Mthfd2 KD E14 mESCs. Additionally, homozygous Mthfd2 knockout (KO) mESCs are characterized by the loss of typical mESC morphology, abnormal expression of marker genes, and compromised cell proliferation. Forced expression of Mthfd2 rescues the Mthfd2 KO-induced differentiation and compromised cell proliferation. In addition, MTHFD2 protein expression is gradually silenced during the differentiation of mESCs into embryoid bodies (EBs). Expression of Mthfd2 facilitates mouse induced pluripotent stem cells (iPSCs)induction, Mthfd2 promotes complete reprogramming of iPSCs and improves the quality of iPSCs. All iPSCs induced with Mthfd2 (OSKM2 iPSCs) show typical mESC-like morphology and express Oct4-driven GFP. Analysis of changes in the transcriptome due to suppression of Mthfd2. Mthfd2 depletion hinders DNA repair in mESCs Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
 Mus musculus 5739
-
additional information MTHFD2 was localized to both the nucleus and mitochondria in mouse embryonic stem cell (mESCs) Mus musculus
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nucleus
-
 Mus musculus 5634
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
5,10-methylenetetrahydrofolate + NAD+ Mus musculus
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 5,10-methenyltetrahydrofolate + NADH + H+
-
 r
additional information Mus musculus MTHFD2 interacts with mitochondrial ETC complex III in mitochondria, mechanism ?
-
-

Organism

Organism UniProt Comment Textmining
Mus musculus P18155
-
-

Source Tissue

Source Tissue Comment Organism Textmining
embryonic stem cell
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 Mus musculus
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
5,10-methylenetetrahydrofolate + NAD+
-
 Mus musculus 5,10-methenyltetrahydrofolate + NADH + H+
-
 r
additional information MTHFD2 interacts with mitochondrial ETC complex III in mitochondria, mechanism Mus musculus ?
-
-

Synonyms

Synonyms Comment Organism
methenyltetrahydrofolate cyclohydrolase
-
 Mus musculus
methylenetetrahydrofolate dehydrogenase (NAD+-dependent)
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 Mus musculus
MTHFD2
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 Mus musculus

Cofactor

Cofactor Comment Organism Structure
NAD+
-
 Mus musculus
NADH
-
 Mus musculus

General Information

General Information Comment Organism
malfunction Mthfd2 knockdown (KD) results in loss of typical stem cell morphology with reduced alkaline phosphatase (AP) staining. Mthfd2 depletion results in differentiation of mESCs. Two MTHFD2-specific inhibitors, MIN and NIT, are used to inhibit MTHFD2 enzymatic activity in mESCs. Both MIN- and MIT-treated mESCs (MImESCs) maintain typical stem cell morphology and pluripotency-associated marker gene expression. Mthfd2 deficiency induces mitochondrial dysfunction by regulating the activity of complex III. The mitochondrial membrane potential (MMP) and ATP production are decreased and cellular ROS levels are increased in Mthfd2 KD mESCs. Mthfd2 depletion hinders DNA repair in mESCs Mus musculus
physiological function Mthfd2 modulates mitochondrial function and DNA repair to maintain the pluripotency of mouse stem cells. The methylenetetrahydrofolate dehydrogenase (NAD+-dependent), methenyltetrahydrofolate cyclohydrolase (Mthfd2), plays an essential role in maintaining embryonic stem cell pluripotency and promoting complete reprogramming of induced pluripotent stem cells. Mechanistically, in mitochondria, Mthfd2 maintains the integrity of the mitochondrial respiratory chain and prevents mitochondrial dysfunction. In the nucleus, Mthfd2 stabilizes the phosphorylation of EXO1 to support DNA end resection and promote homologous recombination repair. Mthfd2 is a dual-function factor in determining the pluripotency of pluripotent stem cells through both mitochondrial and nuclear pathways, ultimately ensuring safe application of pluripotent stem cells. Key role of Mthfd2 in the maintenance of mESC self-renewal. MTHFD2 has nonenzymatic functions in mESCs. MTHFD2 interacts with CDK1 and EXO1 to regulate DNA damage level in mESCs. Mthfd2 modulates homologous recombination repair by regulating EXO1 phosphorylation via affecting the kinase activity of CDK1 to modulate homologous recombination repair and protect genomic integrity Mus musculus