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Revisiting the Crabtree/Warburg effect in a dynamic perspective: a fitness advantage against sugar-induced cell death.

ABSTRACT: The mechanisms behind the Warburg effect in mammalian cells, as well as for the similar Crabtree effect in the yeast Saccharomyces cerevisiae, are still a matter of debate: why do cells shift from the energy-efficient respiration to the energy-inefficient fermentation at high sugar concentration? This review reports on the strong similarities of these phenomena in both cell types, discusses the current ideas, and provides a novel interpretation of their common functional mechanism in a dynamic perspective. This is achieved by analysing another phenomenon, the sugar-induced-cell-death (SICD) occurring in yeast at high sugar concentration, to highlight the link between ATP depletion and cell death. The integration between SICD and the dynamic functioning of the glycolytic process, suggests that the Crabtree/Warburg effect may be interpreted as the avoidance of ATP depletion in those conditions where glucose uptake is higher than the downstream processing capability of the second phase of glycolysis. It follows that the down-regulation of respiration is strategic for cell survival allowing the allocation of more resources to the fermentation pathway, thus maintaining the cell energetic homeostasis.

SUBMITTER: de Alteriis E

PROVIDER: S-EPMC5969562 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Revisiting the Crabtree/Warburg effect in a dynamic perspective: a fitness advantage against sugar-induced cell death.

de Alteriis Elisabetta E Cartenì Fabrizio F Parascandola Palma P Serpa Jacinta J Mazzoleni Stefano S

Cell cycle (Georgetown, Tex.) 20180101 6

The mechanisms behind the Warburg effect in mammalian cells, as well as for the similar Crabtree effect in the yeast Saccharomyces cerevisiae, are still a matter of debate: why do cells shift from the energy-efficient respiration to the energy-inefficient fermentation at high sugar concentration? This review reports on the strong similarities of these phenomena in both cell types, discusses the current ideas, and provides a novel interpretation of their common functional mechanism in a dynamic p ...[more]

PMID: 29509056

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Project description:The discovery of the TROSY effect (Pervushin et al. in Proc Natl Acad Sci USA 94:12366-12371, 1997) for reducing transverse relaxation and line sharpening through selecting pathways in which dipole-dipole and CSA Hamiltonians partially cancel each other had a tremendous impact on solution NMR studies of macromolecules. Together with the methyl TROSY (Tugarinov and Kay in J Biomol NMR 28:165-172, 2004) it enabled structural and functional studies of significantly larger systems. The optimal field strengths for TROSY have been estimated to be on spectrometers operating around 900 MHz (21.14 T) for the 1HN TROSY (Pervushin et al. in Proc Natl Acad Sci USA 94:12366-12371, 1997) while the aromatic 13C (13Caro) TROSY is posited to be optimal at around 600 MHz (14.09 T) (Pervushin et al. in J Am Chem Soc 120:6394-6400, 1998b; Pervushin in Q Rev Biophys 33:161-197, 2000). The initial rational was based on the consideration of where the quadratic B0 field dependences of the TROSY relaxation rates reach a minimum. For sensitivity consideration, however, it is interesting to estimate which field strengths yield the tallest peaks. Recent studies of 15N-detected TROSYs suggested that maximal peak heights are expected at 1.15 GHz (27.01 T) although the slowest relaxation rates or longest transverse relaxation times T2 are indeed expected around 900 MHz (21.14 T) (Takeuchi in J Biomol NMR 63:323-331, 2015; Takeuchi et al. in J Biomol NMR 64:143-151, 2016). This was based on the fact that the heights of Lorentzian lines are proportional to B o3/2 * T2 (Bo). Thus, multiplying the parabolic T2(Bo) dependence with the increasing function of B o3/2 shifts the maxima of peak-height field dependence from the T2 maximum at 900 MHz to higher fields. Moreover, besides shifting the peak height maximum for 15N TROSY, this analysis yields estimates for optimal peak heights for 1HN detected TROSY to 1.5 GHz, and to 900 MHz for 13C-detected 13CaroTROSY as is detailed below. To our knowledge, this aspect of field dependence of TROSY sensitivity has not been in the attention of the NMR community but may affect perspectives of NMR at ultra-high fields.

Dataset Information

Revisiting the Crabtree/Warburg effect in a dynamic perspective: a fitness advantage against sugar-induced cell death.

Publications

Revisiting the Crabtree/Warburg effect in a dynamic perspective: a fitness advantage against sugar-induced cell death.

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