Roles of mitochondrial unfolded protein response in mammalian stem cells

Abstract

The mitochondrial unfolded protein response (UPR mt ) is an evolutionarily conserved adaptive mechanism for improving cell survival under mitochondrial stress. Under physiological and pathological conditions, the UPR mt is the key to maintaining intracellular homeostasis and proteostasis. Important roles of the UPR mt have been demonstrated in a variety of cell types and in cell development, metabolism, and immune processes. UPR mt 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 UPR mt in somatic cells have been widely reported, the roles of the UPR mt in stem cells are not fully understood. The roles and functions of the UPR mt depend on stem cell type. Therefore, this paper summarizes the potential significance of the UPR mt 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.

Activation of the Mitochondrial Unfolded Protein Response: A New Therapeutic Target?

“…Mitochondrial diseases [60,64,73] Parkinson's disease [93][94][95][96]148] Alzheimer's disease [105][106][107][108][109] Huntington's disease [115] Amyotrophic lateral sclerosis [121][122][123][124] Heart diseases [132] Aging [139][140][141][142] Cancer [157,160] Author Contributions:…”

“…Mitochondrial changes in CSCs, including morphological changes, abnormal activation of signaling pathways, mitochondrial dysfunctions, production of ROS, enhanced mitophagy, and UPR mt modulation, are key regulators of CSC proliferation and apoptosis and are also among the reasons for the failure of antitumor treatments [ 159 ]. Therefore, targeting UPRmt in CSCs can be essential for the effective treatment of cancer [ 160 ].…”

Effect and Mechanism of Fuzheng Oral Liquid on Anlotinib Resistance in Non-Small Cell Lung Cancer Cells

“…Cancer cells are often exposed to hypoxia, nutrient deficiencies, oxidative stress and other metabolic dysregulation, resulting in endoplasmic reticulum stress and UPR activation. The UPR is a complex signaling pathway that regulates multiple gene expression at the transcriptional and translational levels and is a fundamental mechanism for maintaining cellular homeostasis [15,16] . Depending on the duration and extent of endoplasmic reticulum stress, the UPR can provide survival signals by activating the adaptive and anti-apoptotic pathway, ERAD or by inducing the cell death program Endoplasmic Reticulum Stress Induced Apoptosis (ERSIA).…”