Bcl-2 expression stimulates ethanol production in yeast.

Abstract

It is now well established that shifts in energy metabolism are associated with cancer development and progression. The most studied of these phenomena is the Warburg effect, which corresponds to an increase of anaerobic glycolysis vs mitochondrial oxidative phosphorylation to produce energy for cellular processes. However, the mechanisms related to these metabolic switches are still a matter of debate. Bcl-2 family proteins contain both pro- (e.g. Bax), and anti-apoptotic (e.g. Bcl-2 and Bcl-xL) members which are respectively encoded by tumor suppressors and proto-oncogenes. Up-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL have been associated with Non-Hodgkin's lymphoma; and certain studies indicate that Bcl-2 family proteins play a role in the regulation of energy metabolism. However, the definition of the molecular mechanisms involved in Bcl-2/xL regulation of carbohydrate metabolism are challenging to define as mammalian cell models contain several Bcl-2/xL homologs with possible redundant functions. The yeast S. cerevisiae is a eukaryotic cell model which possesses the advantages of: (i) to undergo natural carbohydrate metabolic shifts; and (ii) not to possess any Bcl-2 family homologs. A 13C-NMR based detection and quantification of extracellular glucose-derived metabolites allowed us to recently observe that Bcl-2 expression was associated with a significant increase of alcoholic fermentation in yeast. These data suggest that Bcl-2 expression levels may play an active role in the stimulation of lactic fermentation commonly observed in blood cancer cells. These data also suggest that this stimulation of fermentation by Bcl-2 is direct; and that it does not require the support of other Bcl-2 homologs.