Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) and Their Prospective Roles in Kidney Disease

Abstract

Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) serve as essential hubs for interorganelle communication in eukaryotic cells and play multifunctional roles in various biological pathways. A defect in ER-mitochondria signaling or MAMs dysfunction has pleiotropic effects on a variety of intracellular events, which results in disturbances of the mitochondrial quality control system, Ca2+ dyshomeostasis, apoptosis, ER stress, and inflammasome activation, which all contribute to the onset and progression of kidney disease. Here, we review the structure and molecular compositions of MAMs as well as the experimental methods used to study these interorganellar contact sites. We will specifically summarize the downstream signaling pathways regulated by MAMs, mainly focusing on mitochondrial quality control, oxidative stress, ER-mitochondria Ca2+ crosstalk, apoptosis, inflammasome activation, and ER stress. Finally, we will discuss how alterations in MAMs integrity contribute to the pathogenesis of kidney disease and offer directions for future research.

Transmission Electron Microscopy to Follow Ultrastructural Modifications of Erythroblasts Upon ex vivo Human Erythropoiesis

“…Functions of mitochondria are tightly linked to communication among organelles ( Theurey et al, 2016 ; Desai et al, 2020 ; Gao et al, 2020 ; Kohler et al, 2020 ; Yang et al, 2020 ; Strobbe et al, 2021 ). The quantification of MAMs shows no difference from ProE to PolyE.…”

“…At the transition from PolyE to OrthoE, the total of MAM structures per cell decreases together with the percentage of mitochondria forming MAMs ( Figure 4 ). MAMs are well-known structures involved in regulation of calcium homeostasis, lipid synthesis and transfer, mitochondria movement and dynamics, ER stress regulation, inflammation, and autophagy ( Gao et al, 2020 ; Kohler et al, 2020 ; Yang et al, 2020 ). OrthoE stage also corresponds to a stage with drastic changes in cellular functions, where the cell needs to shut down several functions and to prepare for enucleation.…”

Structure and Function of Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) and Their Role in Cardiovascular Diseases

“…MAM was then isolated, and its biochemical functions were examined in the 1990s [18]. The first identification related to the composition of MAMs was performed by Gao et al, using limited proteolysis [19], while the first comprehensive analysis of MAM proteome was performed by Zhang et al [19,20]. Approximately 991 proteins in the MAM fraction were identified.…”

Calcium Signaling Mediates Cell Death and Crosstalk with Autophagy in Kidney Disease

“…The mitochondria contact the ER membrane through the mitochondria-associated membrane (MAM), which provides communication between these two organelles and mediates Ca 2+ transfer from the ER to the mitochondria. Moreover, MAM-mediated ER-mitochondria Ca 2+ crosstalk regulates apoptosis and autophagy, which contributes to the pathogenesis of kidney disease [55]. It has been shown that Ca 2+ redistribution from the ER to the mitochondria regulates apoptosis and autophagy and contributes to lead-induced nephrotoxicity in primary rat proximal tubular cells [56,57].…”