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World J Stem Cells. Jul 26, 2021; 13(7): 737-752
Published online Jul 26, 2021. doi: 10.4252/wjsc.v13.i7.737
Roles of mitochondrial unfolded protein response in mammalian stem cells
Li-Fang Gu, Jia-Qi Chen, Qing-Yin Lin, Yan-Zhou Yang
Li-Fang Gu, Jia-Qi Chen, Qing-Yin Lin, Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Department of Histology and Embryology, School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Yan-Zhou Yang, Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Department of Histology and Embryology, School of Basic Medicine, Ningxia Medical University, Yinchuan 750001, Ningxia Hui Autonomous Region, China,
Author contributions: Gu LF mainly wrote the manuscript; Chen JQ and Lin QY were involved in writing part of the manuscript and preparing the figure; Yang YZ supervised, designed, and revised the manuscript.
Supported by the Key Projects of Natural Science Foundation of Ningxia, No. 2020AAC02020; and the Funds of Ningxia Medical University, No. XY201808.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yan-Zhou Yang, PhD, Professor, Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Department of Histology and Embryology, School of Basic Medicine, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750001, Ningxia Hui Autonomous Region, China. alnord820119@163.com
Received: February 7, 2021
Peer-review started: February 7, 2021
First decision: May 5, 2021
Revised: May 13, 2021
Accepted: June 15, 2021
Article in press: June 15, 2021
Published online: July 26, 2021
Processing time: 166 Days and 12.9 Hours
Abstract

The mitochondrial unfolded protein response (UPRmt) is an evolutionarily conserved adaptive mechanism for improving cell survival under mitochondrial stress. Under physiological and pathological conditions, the UPRmt is the key to maintaining intracellular homeostasis and proteostasis. Important roles of the UPRmt have been demonstrated in a variety of cell types and in cell development, metabolism, and immune processes. UPRmt dysfunction leads to a variety of pathologies, including cancer, inflammation, neurodegenerative disease, metabolic disease, and immune disease. Stem cells have a special ability to self-renew and differentiate into a variety of somatic cells and have been shown to exist in a variety of tissues. These cells are involved in development, tissue renewal, and some disease processes. Although the roles and regulatory mechanisms of the UPRmt in somatic cells have been widely reported, the roles of the UPRmt in stem cells are not fully understood. The roles and functions of the UPRmt depend on stem cell type. Therefore, this paper summarizes the potential significance of the UPRmt in embryonic stem cells, tissue stem cells, tumor stem cells, and induced pluripotent stem cells. The purpose of this review is to provide new insights into stem cell differentiation and tumor pathogenesis.

Keywords: Mitochondrial unfolded protein response; Mammals; Stem cells; Cancer

Core Tip: Mitochondrial unfolded protein response (UPRmt) is a newly discovered equilibrium stress mechanism of mitochondria in the stressed cells to maintain the stressed proteins. Stem cells are a group of cells that have an infinite or eternal ability to self-renew and affect cell differentiation, aging, cancer, etc. Here we discuss the potential significance of UPRmt in stem cells, with an aim to provide a new theoretical basis and therapeutic target for cell differentiation, senescence, and some diseases.