Deciphering the nuclear function of folate enzyme MTHFD2 in cancer: a novel role for nuclear MTHFD2 in mitosis
Subcellular compartmentalisation of metabolic enzymes may elicit specific cellular functions by establishing a unique metabolic environment. Indeed, the nuclear translocation of certain metabolic enzymes impacts epigenetics and gene expression regulation. In this thesis we reveal that, in cancer, th...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/689147 |
| Acceso en línea: | http://hdl.handle.net/10803/689147 |
| Access Level: | acceso abierto |
| Palabra clave: | Folate metabolism Mitosis Methylation Centromere Metabolic compartmentalisation Metabolismo de los folatos Metilación Centrómero Compartimentalización metabólica 575 |
| Sumario: | Subcellular compartmentalisation of metabolic enzymes may elicit specific cellular functions by establishing a unique metabolic environment. Indeed, the nuclear translocation of certain metabolic enzymes impacts epigenetics and gene expression regulation. In this thesis we reveal that, in cancer, the mitochondrial enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) localises in the nucleus during the G2-M phase of the cell cycle to secure mitosis progression. Nuclear MTHFD2 interacts with proteins involved in mitosis regulation and centromere stability. Loss of MTHFD2 induces centromere overexpression and severe hypomethylation, leading to the accumulation of chromosomal aberrations arising from chromosome congression and segregation defects. Blocking the catalytic nuclear function of MTHFD2 recapitulates this phenotype, attributing to nuclear MTHFD2 an active role in controlling mitosis. Our discovery uncovers a nuclear moonlighting role for the cancer target MTHFD2, emphasising that the unconventional localisation of metabolic activities can impact the fate of mitosis. |
|---|