When glucose is available, many organisms repress mitochondrial
respiration in favour of aerobic glycolysis, or fermentation in yeast,
that suffices for ATP production. Fission yeast cells, however, rely
partially on respiration for rapid proliferation under fermentative
conditions. Here, we determined the limiting factors that require
respiratory function during fermentation. When inhibiting the
electron transport chain, supplementation with arginine was
necessary and sufficient to restore rapid proliferation. Accordingly,
a systematic screen for mutants growing poorly without arginine
identified mutants defective in mitochondrial oxidative metabolism. Genetic or pharmacological inhibition of respiration triggered
a drop in intracellular levels of arginine and amino acids derived
from the Krebs cycle metabolite alpha-ketoglutarate: glutamine,
lysine and glutamic acid. Conversion of arginine into these amino
acids was required for rapid proliferation when blocking the
respiratory chain. The respiratory block triggered an immediate
gene expression response diagnostic of TOR inhibition, which was
muted by arginine supplementation or without the AMPK-activating kinase Ssp1. The TOR-controlled proteins featured biased
composition of amino acids reflecting their shortage after respiratory inhibition. We conclude that respiration supports rapid
proliferation in fermenting fission yeast cells by boosting the
supply of Krebs cycle-derived amino acids
