Extracellular pH and high concentration of potassium regulate the primary necrosis in the yeast Saccharomyces cerevisiae.

V A Bidiuk,A I Alexandrov,A Ya Valiakhmetov

doi:10.1007/s00203-021-02708-6

Abstract

Extracellular pH and concentration of K+ as well as their gradient across the plasma membrane have a significant impact on the physiology of the yeast cell, but their role in cell death has not been thoroughly investigated. Here we observed that increasing extracellular pH, as well as supplementing with K+ ions had a mitigating effect on cell death in yeast occurring under several conditions. The first is sugar induced cell death (SICD), and the second is death caused by several specific gene deletions, which have been recently identified in a systematic screen. It was shown that in both cases, primary necrosis is suppressed at neutral pH. SICD was also inhibited by the protonophore dinitrophenol (DNP) and 150mM extracellular K+, with the latter condition also benefiting survival of cell dying due to gene mutations. In the case of SICD, these effects could not be mitigated by perturbing known pH-dependent signaling pathways, and thus are likely to be realized via direct effects on the plasma membrane potential. Thus, (a)-we show that stabilization of external pH at a neutral level can suppress different types of primary necrosis, and (b)-we suggest that changes to the cellular membrane potential can play a central role in yeast cell death caused by different factors.

Highlights

Fungi and yeast are capable of growing over a wide range of extracellular pH
In order to discriminate the effect of ascorbate as a scavenger for reactive oxygen species (ROS) from the buffer effect, we tested the effect of HEPES buffer on sugar induced cell death (SICD) and ROS generation upon incubation of S. cerevisiae yeast with glucose
Yeasts respond to changes in extracellular pH in a complex manner (Arino 2010; Serra-Cardona et al 2015) Basically, this response affects the functioning of the main signaling pathways

Summary

Introduction

Fungi and yeast are capable of growing over a wide range of extracellular pH. In turn, the extracellular pH has a significant effect on the physiology of the fungal cell. Acidic extracellular pH is involved in the regulation of cell death in cancer cells, switching it from apoptosis to necrosis (Meurette et al 2005; Lan et al 2007; Riemann et al 2011). If cell death is thought to occur due to plasma membrane permeabilization, this is termed primary necrosis (CarmonaGutierrez et al 2018). The rupture of the plasma membrane precedes (or occurs together with) the processes of disintegration of intracellular structures. The destruction of intracellular structures occurs while maintaining an intact membrane. In this case, permeabilization of the plasma membrane can occur at the final stage of apoptosis (secondary necrosis). Necrosis can happen without the activation of any enzymes or signaling pathways, while apoptosis always begins with the activation of caspases, followed by the irreversible activation of a number of intracellular mechanisms

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