Dihydroorotate dehydrogenase (DHODH) is the only core de novo pyrimidine enzyme in the mitochondrial inner membrane, coupling nucleotide production to electron transport. Curtabbi et al. show that a cytosolic, fumarate-dependent DHODH orthologue can bypass this dependence, sustaining pyrimidine synthesis and supporting cell growth during respiration failure.
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Acknowledgements
This work is supported by a grant from the US National Institutes of Health (R35GM158171 to I.B.-S.).
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Vidal-Cruchez, O., Ben-Sahra, I. DHODH turns cytosolic, yet cells keep growing. Nat Metab (2026). https://doi.org/10.1038/s42255-026-01466-3
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DOI: https://doi.org/10.1038/s42255-026-01466-3
