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A KDELR-mediated ER-retrieval system modulates mitochondrial functions via the unfolded protein response in fission
Mengdan Zhu1, Zheng Fang1, Yifan Wu1
1MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China; Anhui Key Laboratory of Cellular Dynamics and Chemical Biology & Hefei National Research Center for Interdisciplinary Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Abstract:
KDELR (Erd2 [ER retention defective 2] in yeasts) is a receptor protein that retrieves endoplasmic reticulum (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 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 reactive oxygen species 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.
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