Journal Article

Endoplasmic Reticulum-Mitochondria Crosstalk and Beta-Cell Destruction in Type 1 Diabetes

Vig, Saurabh, Zaldumbide, Arnaud, Lambooij, Joost M., Guigas, Bruno

2021

Overview

Beta-cell destruction in type 1 diabetes (T1D) results from the combined effect of inflammation and recurrent autoimmunity. In response to inflammatory signals, beta-cells engage adaptive mechanisms where the endoplasmic reticulum (ER) and mitochondria act in concert to restore cellular homeostasis. In the recent years it has become clear that this adaptive phase may trigger the development of autoimmunity by the generation of autoantigens recognized by autoreactive CD8 T cells. The participation of the ER stress and the unfolded protein response to the increased visibility of beta-cells to the immune system has been largely described. However, the role of the other cellular organelles, and in particular the mitochondria that are central mediator for beta-cell survival and function, remains poorly investigated. In this review we will dissect the crosstalk between the ER and mitochondria in the context of T1D, highlighting the key role played by this interaction in beta-cell dysfunctions and immune activation, especially through regulation of calcium homeostasis, oxidative stress and generation of mitochondrial-derived factors.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Animals / Apoptosis / Autoantigens / Autoantigens - immunology / Autoantigens - metabolism / Autoimmunity / Beta cells / beta-cell / Bioenergetics / Calcium homeostasis / Calcium Signaling / CD8 antigen / CD8-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - metabolism / Cell activation / Cell Death / Cell survival / Cytochrome / Cytokines - metabolism / Diabetes / Diabetes mellitus (insulin dependent) / Diabetes Mellitus, Type 1 - immunology / Diabetes Mellitus, Type 1 - metabolism / Diabetes Mellitus, Type 1 - pathology / Endoplasmic reticulum / Endoplasmic Reticulum - immunology / Endoplasmic Reticulum - metabolism / Endoplasmic Reticulum - pathology / ER stress / Glucose / Homeostasis / Humans / Immune system / Immunology / Inflammation / Inflammation Mediators - metabolism / Insulin / Insulin-Secreting Cells - immunology / Insulin-Secreting Cells - metabolism / Insulin-Secreting Cells - pathology / Kinases / Lymphocytes T / Mitochondria / Mitochondria - immunology / Mitochondria - metabolism / Mitochondria - pathology / Mitochondrial DNA / Organelles / Oxidative Stress / Permeability / Phosphorylation / Protein folding / Protein synthesis / Proteins / Reactive oxygen species / Type 1 diabetes (T1D)