The structure and function of mitochondria-associated endoplasmic reticulum membranes and their role in pancreatic β-cells dysregulation

Abstract

Membrane trafficking and organelle contact sites are important for regulating cell metabolism and survival. The highly specialized regions of close contacts between mitochondria and endoplasmic reticulum (ER), called mitochondria associated membranes (MAMs), are crucial signaling hubs for the lipid and calcium homeostasis, reactive oxygen species delivery, regulation of autophagy and mitochondrial dynamics. In recent years, MAMs have been the focus of multiple studies for identifying the MAMs proteins and defining their signaling mechanisms. Many studies have proved the importance of MAMs in maintaining the normal function of both organelles. Excessive MAM formation is known to trigger the cascade of pathological events, such as mitochondria calcium overload, aberrant lipid levels, autophagosome formation, and eventually, cell apoptosis. In this article, we focus on the composition and function of MAMs, more specifically, the role of MAMs in Ca2+ uptake, ER stress, mitochondrial fusion and fission and autophagy. The altered interaction between ER and mitochondria results in the amendment of pancreatic tissues, revealing the role of MAMs in glucose homeostasis and the development of diabetes. The development of mitochondrial dysfunction, ER stress and oxidative stress are co-related with β-cell dysfunction. MAMs are likely to play an important role of the functional state regulation in pancreatic cells under pathologies by regulating the signaling of the two organelles and the crosstalk of the two pathological events. It was found that under streptozotocin-induced diabetes, the increased level of mitophagy in pancreatic tissue is connected with tight junctions of MAMs.