Role of mitochondria-associated endoplasmic reticulum membranes in insulin sensitivity, energy metabolism, and contraction of skeletal muscle

Abstract

Skeletal muscle has a critical role in the regulation of the energy balance of the organism, particularly as the principal tissue responsible for insulin-stimulated glucose disposal and as the major site of peripheral insulin resistance (IR), which has been related to accumulation of lipid intermediates, reduced oxidative capacity of mitochondria and endoplasmic reticulum (ER) stress. These organelles form contact sites, known as mitochondria-associated ER membranes (MAMs). This interconnection seems to be involved in various cellular processes, including Ca2+ transport and energy metabolism; therefore, MAMs could play an important role in maintaining cellular homeostasis. Evidence suggests that alterations in MAMs may contribute to IR. However, the evidence does not refer to a specific subcellular location, which is of interest due to the fact that skeletal muscle is constituted by oxidative and glycolytic fibers as well as different mitochondrial populations that appear to respond differently to stimuli and pathological conditions. In this review, we show the available evidence of possible differential responses in the formation of MAMs in skeletal muscle as well as its role in insulin signaling and the beneficial effect it could have in the regulation of energetic metabolism and muscular contraction.

Cardiomyocyte Adaptation to Exercise: K+ Channels, Contractility and Ischemic Injury

“…3) and regulates cytosolic Ca 2 + [96,[104][105][106][107]. Under normal physiological conditions, the ER-mitochondria interaction via domain [Ca 2 + ] provides the necessary physiological coupling between muscle contraction/relaxation and the required mitochondrial ATP necessary for muscle function [108]. The MAM complex is also modulated biochemically by hexokinase II (HKII), and the signaling molecules Akt and the serine/threonine kinase GSK3β further regulate domain Ca 2 + during IR injury or cytoprotection against IR stress [109][110][111].…”

Characterization of differential distribution patterns between mitofusin isoforms and their interaction in developing skeletal muscles of rat

“…The expression of mitofusins (Mfn 1 and Mfn 2) in skeletal muscle is suggested to be associated with mitochondrial dynamics and its proximity to the SR 26,27 ; therefore, we chose to study the fiberspecific distribution pattern of Mfn 1 and Mfn 2 using IHC. In neonate muscles, both mitofusins exhibited expression restricted only to some specific fibers (Figure 3A-C).…”

Zebrafish and cellular models ofSELENON-Related Myopathy exhibit novel embryonic and metabolic phenotypes

“…It has been shown that SelN also colocalizes with Mitochondria Associated Membranes (MAMs) that tether the mitochondria to the ER (Filipe et al, 2021). MAMs allow for Ca 2+ influx from the ER into the mitochondria, phospholipid synthesis and transport, regulation of mitochondrial dynamics, among other vital cell functions (Hemel et al, 2021; Nieblas et al, 2022). Based on these findings, we hypothesize that mitochondria dysregulation may play a vital role in the disease mechanism of SELENON -RM.…”