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Mol. Cells

Published online December 28, 2022

© The Korean Society for Molecular and Cellular Biology

Golgi Stress Response: New Insights into the Pathogenesis and Therapeutic Targets of Human Diseases

Won Kyu Kim1,2 , Wooseon Choi3 , Barsha Deshar3 , Shinwon Kang4,5 , and Jiyoon Kim3,*

1Natural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Korea, 2Division of Bio-Medical Science & Technology, University of Science and Technology (UST), Daejeon 34113, Korea, 3Department of Pharmacology, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea, 4Department of Physiology, University of Toronto, Toronto, ON M5S, Canada, 5Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System, Toronto, ON M5G, Canada

Correspondence to : jykim@catholic.ac.kr

Received: September 27, 2022; Revised: October 24, 2022; Accepted: October 30, 2022

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

Abstract

The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the ‘Golgi stress response,’ which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.

Keywords Golgi stress, Golgi stress response, human disease, pathogenesis, therapeutic target

Article

On-line First

Mol. Cells

Published online December 28, 2022

Copyright © The Korean Society for Molecular and Cellular Biology.

Golgi Stress Response: New Insights into the Pathogenesis and Therapeutic Targets of Human Diseases

Won Kyu Kim1,2 , Wooseon Choi3 , Barsha Deshar3 , Shinwon Kang4,5 , and Jiyoon Kim3,*

1Natural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Korea, 2Division of Bio-Medical Science & Technology, University of Science and Technology (UST), Daejeon 34113, Korea, 3Department of Pharmacology, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea, 4Department of Physiology, University of Toronto, Toronto, ON M5S, Canada, 5Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System, Toronto, ON M5G, Canada

Correspondence to:jykim@catholic.ac.kr

Received: September 27, 2022; Revised: October 24, 2022; Accepted: October 30, 2022

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

Abstract

The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the ‘Golgi stress response,’ which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.

Keywords: Golgi stress, Golgi stress response, human disease, pathogenesis, therapeutic target

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

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