Role of Calcium/Calcineurin Signalling in Regulating Intracellular Reactive Oxygen Species Homeostasis in Saccharomyces cerevisiae.

Guohui Li,Yunying Zhao,Wenxuan Fu,Yu Deng

doi:10.3390/genes12091311

Abstract

The calcium/calcineurin signalling pathway is required for cell survival under various environmental stresses. Using Saccharomyces cerevisiae, we explored the mechanism underlying calcium-regulated homeostasis of intracellular reactive oxygen species (ROS). We found that deletion of acyltransferase Akr1 and C-5 sterol desaturase Erg3 increased the intracellular ROS levels and cell death, and this could be inhibited by the addition of calcium. The hexose transporter Hxt1 and the amino acid permease Agp1 play crucial roles in maintaining intracellular ROS levels, and calcium induced the expression of the HXT1 and AGP1 genes. The cytosolic calcium concentration was decreased in both the akr1Δ and erg3Δ mutants relative to wild-type cells, potentially lowering basal expression of HXT1 and AGP1. Moreover, the calcium/calcineurin signalling pathway also induced the expression of AKR1 and ERG3, indicating that Akr1 and Erg3 might perform functions that help yeast cells to survive under high calcium concentrations. Our results provided mechanistic insight into how calcium regulated intracellular ROS levels in yeast.

Highlights

Calcium ions are intracellular signalling molecules that regulate many cellular processes in eukaryotic cells including programmed cell death, muscle contraction and cell proliferation [1]
C-5 sterol desaturase Erg3 and the integral membrane protein Akr1, which is responsible for palmitoylation of certain target proteins, exhibited elevated intracellular Reactive oxygen species (ROS) levels compared with WT cells (Figure 1A)
Because intracellular ROS levels are closely related to cell death, we wondered whether mutants of AKR1 and ERG3 genes could lead to greater cell death

Summary

Introduction

Calcium ions are intracellular signalling molecules that regulate many cellular processes in eukaryotic cells including programmed cell death, muscle contraction and cell proliferation [1]. The calcium homeostasis system and signalling regulation pathway in yeast cells are conserved, and similar to those in mammalian cardiac muscle cells [4,5]. S. cerevisiae provides powerful genetic and genomic tools for exploring calcium homeostasis and the signal transduction system in yeast cells, and the knowledge may be applicable to higher eukaryotes and useful for curing human diseases, such as pathological heart enlargement and heart failure [6,7]. Glucose activates a series of signal transduction pathways involving G-protein-coupled receptors, hexokinases and transmembrane glucose receptors that work together to inhibit respiration and promote aerobic fermentation [14]

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