A KDELR-mediated ER-retrieval system modulates mitochondrial functions via the unfolded protein response in fission yeast

KDELR (Erd2 in yeasts) is a receptor protein that retrieves ER-resident proteins from the Golgi apparatus. However, the role of the KDELR-mediated ER-retrieval system in regulating cellular homeostasis remains elusive. Here we show that the absence of Erd2 triggers the unfolded protein response (UPR) and enhances mitochondrial respiration and reactive oxygen species (ROS) in an UPR-dependent manner in the fission yeast Schizosaccharomyces Pombe. Moreover, we perform transcriptomic analysis and find that the expression of genes related to mitochondrial respiration and the tricarboxylic acid cycle is upregulated in a UPR-dependent manner in cells lacking Erd2. The increased mitochondrial respiration and ROS production is required for cell survival in the absence of Erd2. Therefore, our findings reveal a novel role of the KDELR/Erd2-mediated ER-retrieval system in modulating mitochondrial functions and highlight its importance for cellular homeostasis in the fission yeast.