ArticleNature communications2024
Inhibition of mitochondrial folate metabolism drives differentiation through mTORC1 mediated purine sensing.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Pralatrexate is a potent pan-serotype human adenovirus inhibitor through suppression of dihydrofolate reductase.Antimicrobial agents and chemotherapy · 2026Article
- Understanding drug resistance in chronic myeloid leukemia through the lens of leukemic stem cell states: insights from single-cell analyses.Haematologica · 2026Review
- MTHFR functions as a metabolic checkpoint in NSCLC through SLC25A26-mediated SHMT2 inhibition.Cell death & disease · 2026Article
- Roles of RRM2 and RRM2B in pyrimidine stress responses and differentiation of acute myeloid leukemia cells.Cell death discovery · 2026Article
- Cellular Anti-Apoptotic Effects of Dapagliflozin in Methotrexate-Induced Liver Toxicity: Bax/Bcl-2/Cyt-C/Cas-9/Cas-3 Signaling Pathway.International journal of molecular sciences · 2026Article
- Article
- SLC46A1 deficiency-mediated folate restriction suppresses colorectal cancer progression through epigenetic-transcriptional reprogramming.Cell death & disease · 2026Article
- A synergistic multi-omics approach: causal sepsis drivers identified in activated CD4Frontiers in cellular and infection microbiology · 2026Article
- Atovaquone-induced oxidative stress activates the pentose phosphate pathway and Immunogenic cell death in ovarian cancer.Scientific reports · 2025Article
- IGF2BP3 redirects glycolytic flux to promote one-carbon metabolism and RNA methylation.Cell reports · 2025Article
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
- Neurokinin 1 receptor inhibition alleviated mitochondrial dysfunctionActa pharmaceutica Sinica. B · 2025Article
- PAICS-Driven Purine Biosynthesis and Its Prognostic Implications in Lung Adenocarcinoma: A Novel Risk Stratification Model and Therapeutic Insights.Current issues in molecular biology · 2025Article
- Purine Metabolism and Dystonia: Perspectives of a Long-Promised Relationship.Annals of neurology · 2025Review
- Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Supporting cell proliferation through nucleotide biosynthesis is an essential requirement for cancer cells. Hence, inhibition of folate-mediated one carbon (1C) metabolism, which is required for nucleotide synthesis, has been successfully exploited in anti-cancer therapy. Here, we reveal that mitochondrial folate metabolism is upregulated in patient-derived leukaemic stem cells (LSCs). We demonstrate that inhibition of mitochondrial 1C metabolism through impairment of de novo purine synthesis has a cytostatic effect on chronic myeloid leukaemia (CML) cells. Consequently, changes in purine nucleotide levels lead to activation of AMPK signalling and suppression of mTORC1 activity. Notably, suppression of mitochondrial 1C metabolism increases expression of erythroid differentiation markers. Moreover, we find that increased differentiation occurs independently of AMPK signalling and can be reversed through reconstitution of purine levels and reactivation of mTORC1. Of clinical relevance, we identify that combination of 1C metabolism inhibition with imatinib, a frontline treatment for CML patients, decreases the number of therapy-resistant CML LSCs in a patient-derived xenograft model. Our results highlight a role for folate metabolism and purine sensing in stem cell fate decisions and leukaemogenesis.
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Registered trials
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