MTHFD2 in healthy and cancer cells: Canonical and non-canonical functions

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• dc.contributor.author Pardo Lorente, Natalia
• dc.contributor.author Sdelci, Sara
• dc.date.accessioned 2025-10-10T15:48:06Z
• dc.date.available 2025-10-10T15:48:06Z
• dc.date.issued 2024
• dc.date.updated 2025-10-10T15:48:06Z
• dc.description.abstract Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial enzyme of the folate-mediated one-carbon metabolism pathway. MTHFD2 has become a highly attractive therapeutic target due to its consistent upregulation in cancer tissues and its major contribution to tumor progression, although it also performs vital functions in proliferating healthy cells. Here, we review the diversity of canonical and non-canonical functions of this key metabolic enzyme under physiological conditions and in carcinogenesis. We provide an overview of its therapeutic potential and describe its regulatory mechanisms. In addition, we discuss the recently described non-canonical functions of MTHFD2 and the mechanistic basis of its oncogenic function. Finally, we speculate on novel therapeutic approaches that take into account subcellular compartmentalization and outline new research directions that would contribute to a better understanding of the fundamental roles of this metabolic enzyme in health and disease.
• dc.format.mimetype application/pdf
• dc.identifier.citation Pardo-Lorente N, Sdelci S. MTHFD2 in healthy and cancer cells: Canonical and non-canonical functions. NPJ Metab Health Dis. 2024 Mar 15;2(1):3. DOI: 10.1038/s44324-024-00005-6
• dc.identifier.doi http://dx.doi.org/10.1038/s44324-024-00005-6
• dc.identifier.issn 2948-2828
• dc.identifier.uri http://hdl.handle.net/10230/71478
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof npj Metabolic Health and Disease. 2024;2(1):3
• dc.rights © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article¿s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article¿s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Cancer
• dc.subject.keyword Cancer metabolism
• dc.subject.keyword Cell biology
• dc.title MTHFD2 in healthy and cancer cells: Canonical and non-canonical functions
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion