Unfolded Protein Response-Dependent Communication and Contact among Endoplasmic Reticulum, Mitochondria, and Plasma Membrane.

Atsushi Saito,Kazunori Imaizumi

doi:10.3390/ijms19103215

Atsushi Saito, Kazunori Imaizumi

Open Access

https://doi.org/10.3390/ijms19103215

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Abstract

The function of the endoplasmic reticulum (ER) can be impaired by changes to the extra- and intracellular environment, such as disruption of calcium homeostasis, expression of mutated proteins, and oxidative stress. In response to disruptions to ER homeostasis, eukaryotic cells activate canonical branches of signal transduction cascades, collectively termed the unfolded protein response (UPR). The UPR functions to remove or recover the activity of misfolded proteins that accumulated in the ER and to avoid irreversible cellular damage. Additionally, the UPR plays unique physiological roles in the regulation of diverse cellular events, including cell differentiation and development and lipid biosynthesis. Recent studies have shown that these important cellular events are also regulated by contact and communication among organelles. These reports suggest strong involvement among the UPR, organelle communication, and regulation of cellular homeostasis. However, the precise mechanisms for the formation of contact sites and the regulation of ER dynamics by the UPR remain unresolved. In this review, we summarize the current understanding of how the UPR regulates morphological changes to the ER and the formation of contact sites between the ER and other organelles. We also review how UPR-dependent connections between the ER and other organelles affect cellular and physiological functions.

Highlights

The endoplasmic reticulum (ER) is the intracellular organelle responsible for the synthesis, folding, modification, and assembly of secretory proteins
Understanding how ER morphology is regulated is essential for understanding how the ER communicates with other organelles. Characterizing this regulation is important for comprehending cellular homeostasis because a well-developed ER that spans the cytoplasm frequently changes its morphology and plays roles in bidirectional signal transmission through the formation of contact sites
These organelle contacts regulate the dynamics of each organelle and signal transduction, and orchestrate cellular homeostasis and biological functions

Summary

Introduction

The endoplasmic reticulum (ER) is the intracellular organelle responsible for the synthesis, folding, modification, and assembly of secretory proteins. This organelle has a unique system that maintains an optimal environment for protein quality control and is collectively known as the unfolded protein response (UPR) [1,2]. The function of the UPR has been extended from maintenance of protein quality control to include fine-tuning of cellular homeostasis and biological functions, such as cell development, differentiation, glycogenesis, and lipid metabolism [5,6,7,8,9,10]. We discuss current knowledge of the diverse functions and prospects of the UPR for regulating ER morphology and the formation of contact sites with mitochondria and the plasma membrane (PM)

ER Stress Transducers and Key Molecules of the UPR

Morphological Changes to the ER by the UPR

Concluding Remarks