• JASWANDI UJWAL DANDEKAR

      Articles written in Journal of Biosciences

    • Fermentative metabolism impedes p53-dependent apoptosis in a Crabtree-positive but not in Crabtree-negative yeast

      ABHAY KUMAR JASWANDI UJWAL DANDEKAR PAIKE JAYADEVA BHAT

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      Tumour cells distinguish from normal cells by fermenting glucose to lactate in presence of sufficient oxygen and functionalmitochondria (Warburg effect). Crabtree effect was invoked to explain the biochemical basis of Warburg effect by suggestingthat excess glucose suppresses mitochondrial respiration. It is known that the Warburg effect and Crabtree effect aredisplayed by Saccharomyces cerevisiae, during growth on abundant glucose. Beyond this similarity, it was also demonstratedthat expression of human pro-apoptotic proteins in S. cerevisiae such as Bax and p53 caused apoptosis. Here, wedemonstrate that p53 expression in S. cerevisiae (Crabtree-positive yeast) causes increase in ROS levels and apoptosis whencells are growing on non-fermentable carbon sources but not on fermentable carbon sources, a feature similar to tumourcells. In contrast, in Kluyveromyces lactis (Crabtree-negative yeast) p53 causes increase in ROS levels and apoptosisregardless of the carbon source. Interestingly, the increased ROS levels and apoptosis are correlated to increased oxygenuptake in both S. cerevisiae and K. lactis. Based on these results, we suggest that at least in yeast, fermentation per se doesnot prevent the escape from apoptosis. Rather, the Crabtree effect plays a crucial role in determining whether the cellsshould undergo apoptosis or not.

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