biostudies-literatureAlam SCancer Research UKFrancis Crick InstituteShimane UniversityIndiana UniversityVersus ArthritisMedical Research CouncilNational Cancer InstituteWellcome TrustBiotechnology and Biological Sciences Research Council2175-2186.e5https://www.ebi.ac.uk/biostudies/studies/S-EPMC7615655biostudies-literatureUnknown33(11)Most eukaryotes respire oxygen, using it to generate biomass and energy. However, a few organisms have lost the capacity to respire. Understanding how they manage biomass and energy production may illuminate the critical points at which respiration feeds into central carbon metabolism and explain possible routes to its optimization. Here, we use two related fission yeasts, Schizosaccharomyces pombe and Schizosaccharomyces japonicus, as a comparative model system. We show that although S. japonicus does not respire oxygen, unlike S. pombe, it is capable of efficient NADH oxidation, amino acid synthesis, and ATP generation. We probe possible optimization strategies through the use of stable isotope tracing metabolomics, mass isotopologue distribution analysis, genetics, and physiological expCurrent biology : CBOptimization of energy production and central carbon metabolism in a non-respiring eukaryote.PMC7615655220790/Z/20/Z103741/Z/14/ZBB/T000481/1CC0102103741Alam SGu YBahler JReichert POliferenko SfalseOptimization of energy production and central carbon metabolism in a non-respiring eukaryote.Most eukaryotes respire oxygen, using it to generate biomass and energy. However, a few organisms have lost the capacity to respire. Understanding how they manage biomass and energy production may illuminate the critical points at which respiration feeds into central carbon metabolism and explain possible routes to its optimization. Here, we use two related fission yeasts, Schizosaccharomyces pombe and Schizosaccharomyces japonicus, as a comparative model system. We show that although S. japonicus does not respire oxygen, unlike S. pombe, it is capable of efficient NADH oxidation, amino acid synthesis, and ATP generation. We probe possible optimization strategies through the use of stable isotope tracing metabolomics, mass isotopologue distribution analysis, genetics, and physiological exp2023-01-01T00:00:00Z2023 Jun2025-04-04T07:45:13.235Z2025-04-04T07:45:13.235ZS-EPMC76156553716401710.1016/j.cub.2023.04.046