Less is more or more is less: Implications of glucose metabolism in the regulation of the reproductive potential and total lifespan of the Saccharomyces cerevisiae yeast

Abstract

Carbohydrates are dietary nutrients that have an influence on cells physiology, cell reproductive capacity and, consequently, the lifespan of organisms. They are used in cellular processes after conversion to glucose, which is the primary source of energy and carbon skeleton for biosynthetic processes. Studies of the influence of glucose on cellular parameters and lifespan of organisms are primarily concerned with the effect of low glucose concentration defined as calorie restriction conditions. However, the effect of high glucose concentration on cell physiology is also very important. Thus, a comparative analysis of the effects of low and high glucose concentration conditions on cell efficiency was proposed with regard to reproductive capacity and total lifespan of the cell. Glucose concentration determines the type of metabolism and biosynthetic capabilities, which in turn, through the regulation on the cell size, may affect the reproductive capacity of cells. This study was conducted on yeast cells of wild‐type and mutant strains Δgpa2 and Δgpr1 with glucose signalling pathway impairment. Such an experimental model enabled testing both the role of glucose concentration in the regulation of metabolic changes and the extent to which these changes depend on the extracellular or intracellular glucose concentrations. It has been shown here that calorie/glucose excess connected with changes in cell metabolic fluxes increases biosynthetic capabilities of yeast cells. This leads to an increase in cell dry weight accompanied by the increase in cell size and a simultaneous decrease in the reproductive potential and the overall length of cell life.

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

“…Hence, the difference between the WT and Δ hxk2 strains is the result of the decreased reproductive potential observed for the WT strain under conditions with higher glucose concentration, in particular under CE conditions ( Figure 1 C). These results are in agreement with our previous findings [ 7 ] and support the assumption that the Δ hxk2 strain can be treated as a CR-mimetic strain.…”

“…The carbon/metabolic flux is a crucial response mechanism to changes in nutrient availability, which is directly connected with cell reproductive capacity by influencing physiological efficiency of cells. As we previously reported, although calorie excess significantly decreases reproductive potential and total lifespan of yeast cells, the decreased activity of cAMP-PKA pathway (deletion of Gpa2p and Gpr1p) reduces these changes [ 7 ].…”

“…Furthermore, the reproductive potential data observed in the Δ hxk2 strain ( Figure 1 A–C) and in the previously analyzed Δ gpa2 and Δ grp1 strains point out to a significant role of the cAMP/PKA pathway in proliferative capacity of the cell. It is worth mentioning that, besides genetic alteration, lower activity of the cAMP/PKA pathway can also be obtained by lower availability of glucose concentration [ 7 ] and (this study).…”

“…The reproductive potential of yeast cells is limited, and both genetic and environmental factors have an impact on this parameter. For instance, mutations in numerous genes increase or decrease the numerical value of reproductive potential [ 2 , 3 , 4 ]; also, changes in nutrient content in the medium lead to substantial increase (e.g., in the calorie restriction condition) [ 5 , 6 ] or decrease (e.g., in the conditions of glucose excess) [ 7 ] of that potential. Cell size and the rate of cell size increase per generation also play an important role in the regulation of reproductive potential [ 8 , 9 , 10 , 11 ].…”

Fluctuations in glucose availability prevent global proteome changes and physiological transition during prolonged chemostat cultivations of Saccharomyces cerevisiae

“…Intermittent fasting and reduction of calorie intake in general has been shown to increase healthy lifespan, extend longevity, and reduce oxidative stress in many organisms including S. cerevisiae (Fontana & Partridge, 2015; Longo & Mattson, 2014; Maslanka & Zadrag‐Tecza, 2019). The cells experience the imposed fluctuations in glucose availability in our two‐compartment system as intermittent fasting.…”