MTHFD2: A Retrospective and a Glance into the Future
The 1985 confirmation by Mejia and MacKenzie of mammalian NAD-dependent methylenetetrahydrofolate dehydrogenase activity launched four decades of research on methylenetetrahydrofolate dehydrogenase (NAD<sup>+</sup>-dependent), methenyltetrahydrofolate cyclohydrolase 2 (MTHFD2). This review provides a retrospective on four decades of advancements on MTHFD2 that have revealed its key roles in the folate pathway, amino acid and redox homeostasis, and the metabolism of cancer and immune cells. We trace the initial biochemical characterization of the enzyme, highlight pivotal discoveries regarding MTHFD2's metabolic and non-canonical roles, and discuss the current state of knowledge and future prospects.
Authors
- Costas Koufaris (ORCID: https://orcid.org/0000-0002-1222-5130)
- Vicky Nicolaidou (ORCID: https://orcid.org/0000-0003-1017-2677)
Institutions
- University of Nicosia (CY)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-11-14
- DOI
- https://doi.org/10.3390/ijms262211025
- Primary Topic
- Folate and B Vitamins Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00