In fission yeast, 65 non-essential mitochondrial proteins related to respiration and stress become essential in low-glucose conditions

Mitochondria perform critical functions, including respiration, ATP production, small molecule metabolism, anti-oxidation, and they are involved in a number of human diseases. While the mitochondrial genome contains a small number of protein-coding genes, the vast majority of mitochondrial proteins are encoded by nuclear genes. In fission yeast, Schizosaccharomyces pombe, we screened 457 deletion (del) mutants deficient in nuclear-encoded mitochondrial proteins, searching for those that fail to form colonies in culture medium containing low glucose (0.03–0.1%; low-glucose sensitive, lgs), but that proliferate in regular 2–3% glucose medium. Sixty-five (14%) of the 457 deletion mutants displayed the lgs phenotype. Thirty-three of them are defective either in dehydrogenases, subunits of respiratory complexes, the TCA cycle, or in one of the 9 steps of the CoQ10 biosynthetic pathway. The remaining 32 lgs mutants do not seem to be directly related to respiration. Fifteen are implicated in translation, and 6 encode transporters. The remaining 11 function in anti-oxidation, amino acid synthesis, repair of DNA damage, microtubule cytoskeleton, intracellular mitochondrial distribution, or unknown functions. These 32 diverse lgs genes collectively maintain mitochondrial functions under low (1/20~1/60x normal) glucose concentrations. Interestingly, 30 of them have homologs associated with human diseases.