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) 20452322 (eISSN)
Vol. 6 Art. no. 27942- 27942Areas of Advance
Life Science Engineering (2010-2018)
Subject Categories
Bioinformatics and Systems Biology
DOI
10.1038/srep27942
PubMed
27305947