Reproductive Potential of Yeast Cells Depends on Overall Action of Interconnected Changes in Central Carbon Metabolism, Cellular Biosynthetic Capacity, and Proteostasis.

Roman Maslanka,Renata Zadrag-Tecza

doi:10.3390/ijms21197313

Roman Maslanka, Renata Zadrag-Tecza

Open Access

https://doi.org/10.3390/ijms21197313

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Abstract

Carbon metabolism is a crucial aspect of cell life. Glucose, as the primary source of energy and carbon skeleton, determines the type of cell metabolism and biosynthetic capabilities, which, through the regulation of cell size, may affect the reproductive capacity of the yeast cell. Calorie restriction is considered as the most effective way to improve cellular physiological capacity, and its molecular mechanisms are complex and include several nutrient signaling pathways. It is widely assumed that the metabolic shift from fermentation to respiration is treated as a substantial driving force for the mechanism of calorie restriction and its influence on reproductive capabilities of cells. In this paper, we propose another approach to this issue based on analysis the connection between energy-producing and biomass formation pathways which are closed in the metabolic triangle, i.e., the respiration-glycolysis-pentose phosphate pathway. The analyses were based on the use of cells lacking hexokinase 2 (∆hxk2) and conditions of different glucose concentration corresponding to the calorie restriction and the calorie excess. Hexokinase 2 is the key enzyme involved in central carbon metabolism and is also treated as a calorie restriction mimetic. The experimental model used allows us to explain both the role of increased respiration as an effect of calorie restriction but also other aspects of carbon metabolism and the related metabolic flux in regulation of reproductive potential of the cells. The obtained results reveal that increased respiration is not a prerequisite for reproductive potential extension but rather an accompanying effect of the positive role of calorie restriction. More important seems to be the changes connected with fluxes in central carbon metabolic pathways resulting in low biosynthetic capabilities and improved proteostasis.

Highlights

Cell growth and reproduction are important cell properties in unicellular and multicellular organisms alike
Lack of Hexokinase 2 Prevents Decrease in Reproductive Potential Caused by Increasing Glucose Concentration
In order to explore the links between central carbon metabolism and proliferative capacity of the cells, analyses of reproductive potential in ∆hxk2 mutant under conditions of different glucose concentration (CR—0.5%; optimal—2% and calorie excess (CE)—4%) were performed

Summary

Introduction

Cell growth and reproduction are important cell properties in unicellular and multicellular organisms alike. In the case of yeast cells, the ability to reproduce, or reproductive potential, is expressed by the number of daughter cells produced by the mother cell during her lifetime [1]. The reproductive potential of yeast cells is limited, and both genetic and environmental factors have an impact on this parameter. Cell size and the rate of cell size increase per generation play an important role in the regulation of reproductive potential [8,9,10,11]. Those parameters may be modulated, among others, by nutrient content [12,13]

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