Respiratory metabolism and calorie restriction relieve persistent endoplasmic reticulum stress induced by calcium shortage in yeast
Journal article, 2016

Calcium homeostasis is crucial to eukaryotic cell survival. By acting as an enzyme cofactor and a second messenger in several signal transduction pathways, the calcium ion controls many essential biological processes. Inside the endoplasmic reticulum (ER) calcium concentration is carefully regulated to safeguard the correct folding and processing of secretory proteins. By using the model organism Saccharomyces cerevisiae we show that calcium shortage leads to a slowdown of cell growth and metabolism. Accumulation of unfolded proteins within the calcium-depleted lumen of the endoplasmic reticulum (ER stress) triggers the unfolded protein response (UPR) and generates a state of oxidative stress that decreases cell viability. These effects are severe during growth on rapidly fermentable carbon sources and can be mitigated by decreasing the protein synthesis rate or by inducing cellular respiration. Calcium homeostasis, protein biosynthesis and the unfolded protein response are tightly intertwined and the consequences of facing calcium starvation are determined by whether cellular energy production is balanced with demands for anabolic functions. Our findings confirm that the connections linking disturbance of ER calcium equilibrium to ER stress and UPR signaling are evolutionary conserved and highlight the crucial role of metabolism in modulating the effects induced by calcium shortage.

Author

Stefano Busti

SYSBIO

University of Milano-Bicocca

Valeria Mapelli

Chalmers, Biology and Biological Engineering, Industrial Biotechnology

University of Milano-Bicocca

Farida Tripodi

University of Milano-Bicocca

SYSBIO

Rossella Sanvito

University of Milano-Bicocca

Fulvio Magni

University of Milano-Bicocca

Paola Coccetti

SYSBIO

University of Milano-Bicocca

Marcella Rocchetti

University of Milano-Bicocca

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Lilia Alberghina

SYSBIO

University of Milano-Bicocca

Marco Vanoni

SYSBIO

University of Milano-Bicocca

Scientific Reports

2045-2322 (ISSN)

Vol. 6 Art. no. 27942- 27942

Areas of Advance

Life Science Engineering

Subject Categories

Bioinformatics and Systems Biology

DOI

10.1038/srep27942

PubMed

27305947

More information

Latest update

7/23/2018