Pardo Lorente, NataliaGkanogiannis, AnestisCozzuto, LucaGañez-Zapater, AntoniEspinar, LorenaGhose, RitobrataSeverino, Jacqueline, 1990-García-López, LauraAydin, Rabia GülMartin, LauraNeguembor, Maria VictoriaDarai, EvangeliaCosma, Maria PiaBatlle Morera, LauraPonomarenko, JuliaSdelci, Sara2025-01-312025-01-312024Pardo-Lorente N, Gkanogiannis A, Cozzuto L, Gañez Zapater A, Espinar L, Ghose R, et al. Nuclear localization of MTHFD2 is required for correct mitosis progression. Nat Commun. 2024 Nov 12;15(1):9529. DOI: 10.1038/s41467-024-51847-z2041-1723http://hdl.handle.net/10230/69404Subcellular compartmentalization of metabolic enzymes establishes a unique metabolic environment that elicits specific cellular functions. Indeed, the nuclear translocation of certain metabolic enzymes is required for epigenetic regulation and gene expression control. Here, we show that the nuclear localization of the mitochondrial enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) ensures mitosis progression. Nuclear MTHFD2 interacts with proteins involved in mitosis regulation and centromere stability, including the methyltransferases KMT5A and DNMT3B. Loss of MTHFD2 induces severe methylation defects and impedes correct mitosis completion. MTHFD2 deficient cells display chromosome congression and segregation defects and accumulate chromosomal aberrations. Blocking the catalytic nuclear function of MTHFD2 recapitulates the phenotype observed in MTHFD2 deficient cells, whereas restricting MTHFD2 to the nucleus is sufficient to ensure correct mitotic progression. Our discovery uncovers a nuclear role for MTHFD2, supporting the notion that translocation of metabolic enzymes to the nucleus is required to meet precise chromatin needs.application/pdfeng© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, 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 you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. 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-nc-nd/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-024-51847-zEpigeneticsHistone post-translational modificationsMitosisinfo:eu-repo/semantics/openAccess