Mitochondria-Associated Endoplasmic Reticulum Membranes: Inextricably Linked with Autophagy Process

Abstract

Mitochondria-associated membranes (MAMs), physical connection sites between the endoplasmic reticulum (ER) and the outer mitochondrial membrane (OMM), are involved in numerous cellular processes, such as calcium ion transport, lipid metabolism, autophagy, ER stress, mitochondria morphology, and apoptosis. Autophagy is a highly conserved intracellular process in which cellular contents are delivered by double-membrane vesicles, called autophagosomes, to the lysosomes for destruction and recycling. Autophagy, typically triggered by stress, eliminates damaged or redundant protein molecules and organelles to maintain regular cellular activity. Dysfunction of MAMs or autophagy is intimately associated with various diseases, including aging, cardiovascular, infections, cancer, multiple toxic agents, and some genetic disorders. Increasing evidence has shown that MAMs play a significant role in autophagy development and maturation. In our study, we concentrated on two opposing functions of MAMs in autophagy: facilitating the formation of autophagosomes and inhibiting autophagy. We recognized the link between MAMs and autophagy in the occurrence and progression of the diseases and therefore collated and summarized the existing intrinsic molecular mechanisms. Furthermore, we draw attention to several crucial data and open issues in the area that may be helpful for further study.

FUNDC1 alleviates doxorubicin-induced cardiotoxicity by restoring mitochondrial-endoplasmic reticulum contacts and blocked autophagic flux

“…For the first time, we described the disruptive MERCs formation and compromised MERCs function in DOX-treated cardiomyocytes. Since MERCs were reported as the sites where autophagosomes form, a variety of studies have verified the regulatory role of MERCs tethering proteins in autophagy 33 . PACS2, one of tethering protein of MERCs was reported to promote the formation of mitophagosome in vascular smooth muscle cell and renal tubule cell 34 , 35 .…”

Mitochondria: A Promising Convergent Target for the Treatment of Amyotrophic Lateral Sclerosis

“…This accumulation is facilitated by microdomains adjacent to endoplasmic reticulum (ER) subcompartments that physically interact with mitochondria, referred to as endoplasmic reticulum-mitochondria-associated membranes (MAMs) (reviewed in [255]). MAMs have also been demonstrated to play a crucial role in regulating autophagy and mitochondrial dynamics through the modulation of Drp1 or Mfn2 [256,257]. These complex structures are composed of numerous proteins from both mitochondria and the ER, with additional components yet to be identified [258].…”

Calcium’s Role in Orchestrating Cancer Apoptosis: Mitochondrial-Centric Perspective

“…Calcium signaling begins with the release of calcium ions from internal reservoirs, like the ER. Mitochondria-associated membranes (MAMs) are specialized microdomains where the ER and mitochondria come into close contact [8,9]. MAMs play essential functions in diverse cellular activities, such as fat metabolism and calcium equilibrium, and communication between the two organelles.…”