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Fermentative metabolism impedes p53-dependent apoptosis in a Crabtree-positive but not in Crabtree-negative yeast.
- Source :
-
Journal of biosciences [J Biosci] 2017 Dec; Vol. 42 (4), pp. 585-601. - Publication Year :
- 2017
-
Abstract
- Tumour cells distinguish from normal cells by fermenting glucose to lactate in presence of sufficient oxygen and functional mitochondria (Warburg effect). Crabtree effect was invoked to explain the biochemical basis of Warburg effect by suggesting that excess glucose suppresses mitochondrial respiration. It is known that the Warburg effect and Crabtree effect are displayed by Saccharomyces cerevisiae , during growth on abundant glucose. Beyond this similarity, it was also demonstrated that expression of human pro-apoptotic proteins in S. cerevisiae such as Bax and p53 caused apoptosis. Here, we demonstrate that p53 expression in S. cerevisiae (Crabtree-positive yeast) causes increase in ROS levels and apoptosis when cells are growing on non-fermentable carbon sources but not on fermentable carbon sources, a feature similar to tumour cells. In contrast, in Kluyveromyces lactis (Crabtree-negative yeast) p53 causes increase in ROS levels and apoptosis regardless of the carbon source. Interestingly, the increased ROS levels and apoptosis are correlated to increased oxygen uptake in both S. cerevisiae and K. lactis . Based on these results, we suggest that at least in yeast, fermentation per se does not prevent the escape from apoptosis. Rather, the Crabtree effect plays a crucial role in determining whether the cells should undergo apoptosis or not.
- Subjects :
- Apoptosis genetics
Carbon metabolism
Ethanol metabolism
Ethanol pharmacology
Fermentation
Glucose pharmacology
Glycolysis drug effects
Glycolysis genetics
Humans
Kluyveromyces drug effects
Kluyveromyces metabolism
Metabolic Engineering
Mitochondria drug effects
Mitochondria metabolism
Oxidative Phosphorylation drug effects
Oxygen metabolism
Oxygen pharmacology
Reactive Oxygen Species metabolism
Saccharomyces cerevisiae drug effects
Saccharomyces cerevisiae metabolism
Transgenes
Tumor Suppressor Protein p53 metabolism
bcl-2-Associated X Protein metabolism
Gene Expression Regulation, Fungal
Glucose metabolism
Kluyveromyces genetics
Saccharomyces cerevisiae genetics
Tumor Suppressor Protein p53 genetics
bcl-2-Associated X Protein genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0973-7138
- Volume :
- 42
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of biosciences
- Publication Type :
- Academic Journal
- Accession number :
- 29229877
- Full Text :
- https://doi.org/10.1007/s12038-017-9717-2