Regulation of respiratory growth by Ras: The glyoxylate cycle mutant, cit2Δ, is suppressed by RAS2

In Saccharomyces cerevisiae the Ras/cAMP/PKA signalling pathway controls multiple metabolic pathways, and alterations in the intracellular concentrations of cAMP through modification of signalling pathway factors can be lethal or result in severe growth defects. In this work, the important role of Ras2p in metabolic regulation during growth on the non-fermentable carbon source glycerol is further investigated. The data show that the overexpression of RAS2 suppresses the growth defect of the glyoxylate cycle citrate synthase mutant, cit2Δ. The overexpression results in enhanced proliferation and biomass yield when cells are grown on glycerol as sole carbon source, and increases citrate synthase activity and intracellular citrate concentration. Interestingly, the suppression of cit2Δ and the enhanced proliferation and biomass yield are only observed when RAS2 is overexpressed and not in strains containing the constitutively active allele RAS2 ^val19. However, both RAS2 and RAS2 ^val19upregulated citrate synthase activity. We propose that the RAS2 overexpression results in a combination of general upregulation of respiratory growth capacity and an increase in mitochondrial citrate/ citrate synthases, which together, complement the metabolic requirements of the cit2Δ mutant. The data therefore provide new evidence for the role of Ras2p as a powerful modulator of metabolism during growth on a non-fermentable carbon source.