TCA cycle‐independent acetate metabolism via the glyoxylate cycle in Saccharomyces cerevisiae

Abstract

In Saccharomyces cerevisiae, the accepted theory is that due to TCA cycle dysfunction, the cit1 mutant lacking the mitochondrial enzyme citrate synthase (Cit1) cannot grow on acetate, regardless of the presence of the peroxisomal isoenzyme (Cit2). In this study, we re-evaluated the roles of Cit1 and Cit2 in acetate utilization and examined the pathway of acetate metabolism by analysing mutants defective in TCA or glyoxylate cycle enzymes. Although cit1 cells showed significantly reduced growth on rich acetate medium (YPA), they exhibited growth similar to cit2 and the wild-type cells on minimal acetate medium (YNBA). Impaired acetate utilization by cit1 cit2 cells on YNBA was restored by ectopic expression of either Cit2 or its cytoplasmically localized variants. Deletion of any of the genes for the enzymes solely involved in the TCA cycle (IDH1, KGD1 and LSC1 ), except for SDH1, caused little defect in acetate utilization on YNBA but resulted in significant growth impairment on YPA. In contrast, cells lacking any of the genes involved in the glyoxylate cycle (ACO1, FUM1, MLS1, ICL1 and MDH2 ) did not grow on either YNBA or YPA. Deletion of SFC1 encoding the succinate-fumarate carrier also caused similar growth defects on YNBA. Our results suggest that in S. cerevisiae the glyoxylate cycle functions as a competent metabolic pathway for acetate utilization on YNBA, while both the TCA and glyoxylate cycles are essential for growth on YPA.

Exposure of ELF-EMF and RF-EMF Increase the Rate of Glucose Transport and TCA Cycle in Budding Yeast

“…The glycolytic pathway and TCA cycle are two of the most important metabolic pathways in living organisms, generating reducing factors that drive the production of energy (Lee et al, 2011). We analyzed the transcription levels of genes related to glucose transporters, the glycolytic pathway and TCA cycle through RT-qPCR under ELF-EMF (Table 3) and RF-EMF (Table 4) exposure conditions.…”

“…In addition to propelling the production of energy, the TCA cycle also produces reservoirs of essential metabolic precursors that are channeled toward the biogenesis of essential compounds such as amino acids, fatty acids and carbohydrates (Lee et al, 2011). This cycle can be modified, and enzymes can be upregulated or downregulated depending on the needs of the cell.…”

Recent developments in microbial oils production: a possible alternative to vegetable oils for biodiesel without competition with human food?

“…Five putative genes coding for monocarboxylate permeases (for acetate, lactate or propionate) were identified, one of which was homologous with a Y. lipolityca gene encoding an acetate sensitive gene (Paiva et al 2004). Acetate is rapidly converted into acetyl-CoA by a cytosolic acetyl-CoA synthetase (Lee et al 2011) and then utilisation of acetyl-CoA facilitates glyoxylate cycle.…”

Rewiring yeast acetate metabolism through MPC1 loss of function leads to mitochondrial damage and decreases chronological lifespan

“…This is an anaplerotic device of the TCA cycle which allows the formation of C4 units from C2 units (acetate) by bypassing oxidative decarboxylation (Fig. 4A) 30. At/after the diauxic shift, a clear global decrease was observed for all three intermediates in the mpc1 ∆ cells compared with the wt counterparts (Fig.…”

“…4A). Similarly, the major fate of cytosolic succinate is assumed to be its transfer into mitochondria 30. Moreover, its transport by the Sfc1 carrier provides cytosolic fumarate for conversion to malate which can be used for gluconeogenesis 33.…”