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Fermentative metabolism impedes p53-dependent apoptosis in a Crabtree-positive but not in Crabtree-negative yeast.
J Biosci. 2017 Dec; 42(4):585-601.JB

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.

Authors+Show Affiliations

Kumar A
Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi 110 029, India.
Dandekar JU
No affiliation info available
Bhat PJ
No affiliation info available

MeSH

ApoptosisCarbonEthanolFermentationGene Expression Regulation, FungalGlucoseGlycolysisHumansKluyveromycesMetabolic EngineeringMitochondriaOxidative PhosphorylationOxygenReactive Oxygen SpeciesSaccharomyces cerevisiaeTransgenesTumor Suppressor Protein p53bcl-2-Associated X Protein

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29229877

Citation

Kumar, Abhay, et al. "Fermentative Metabolism Impedes P53-dependent Apoptosis in a Crabtree-positive but Not in Crabtree-negative Yeast." Journal of Biosciences, vol. 42, no. 4, 2017, pp. 585-601.
Kumar A, Dandekar JU, Bhat PJ. Fermentative metabolism impedes p53-dependent apoptosis in a Crabtree-positive but not in Crabtree-negative yeast. J Biosci. 2017;42(4):585-601.
Kumar, A., Dandekar, J. U., & Bhat, P. J. (2017). Fermentative metabolism impedes p53-dependent apoptosis in a Crabtree-positive but not in Crabtree-negative yeast. Journal of Biosciences, 42(4), 585-601.
Kumar A, Dandekar JU, Bhat PJ. Fermentative Metabolism Impedes P53-dependent Apoptosis in a Crabtree-positive but Not in Crabtree-negative Yeast. J Biosci. 2017;42(4):585-601. PubMed PMID: 29229877.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fermentative metabolism impedes p53-dependent apoptosis in a Crabtree-positive but not in Crabtree-negative yeast. AU - Kumar,Abhay, AU - Dandekar,Jaswandi Ujwal, AU - Bhat,Paike Jayadeva, PY - 2017/12/13/entrez PY - 2017/12/13/pubmed PY - 2018/7/22/medline SP - 585 EP - 601 JF - Journal of biosciences JO - J Biosci VL - 42 IS - 4 N2 - 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. SN - 0973-7138 UR - https://www.unboundmedicine.com/medline/citation/29229877/Fermentative_metabolism_impedes_p53_dependent_apoptosis_in_a_Crabtree_positive_but_not_in_Crabtree_negative_yeast_ DB - PRIME DP - Unbound Medicine ER -