Metabolic Side Hustle

The bright red nuclei of these proliferating human colon cells are the result of chemically highlighting (staining) a metabolic enzyme called methylenetetrahydrofolate dehydrogenase 2 (MTHFD2). The surprising thing about this enzyme – aside from its mouth-filling moniker – is that it shouldn’t be in the nucleus at all. MTHFD2 is a well-characterized mitochondrial factor responsible for carrying out what was thought to be solely mitochondrial based metabolism. Research has shown, however, that in proliferating cells MTHFD2 becomes more abundant and translocates to the nucleus. Furthermore, the enzyme’s metabolic activity within the nucleus is crucial for cell division – in experiments where MTHFD2’s nuclear activity was prevented but its mitochondrial activity permitted, cell proliferation ceased. MTHFD2 joins a list of metabolic enzymes that can be found moonlighting in the nucleus. Indeed, nuclear metabolism is a growing field of biology that is shaking up the previously accepted tenets of cell compartmentalisation.

Written by Ruth Williams

Ruth Williams

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Ruth is a freelance science journalist based in the US. She's a regular correspondent for The Scientist, and her work has appeared in The Lancet, Nature, Scientific American Mind, BBC Focus and elsewhere. Twitter @rooph

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• Image by Natalia Pardo Lorente/Centro de Regulación Genómica
• Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
• Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)
• Research published in Nature Communications, November 2024