Cell death regulation by MAMs: from molecular mechanisms to therapeutic implications in cardiovascular diseases

The endoplasmic reticulum (ER) and mitochondria are interconnected intracellular organelles with vital roles in the regulation of cell signaling and function. While the ER participates in a number of biological processes including lipid biosynthesis, Ca2+ storage and protein folding and processing, mitochondria are highly dynamic organelles governing ATP synthesis, free radical production, innate immunity and apoptosis. Interplay between the ER and mitochondria plays a crucial role in regulating energy metabolism and cell fate control under stress. The mitochondria-associated membranes (MAMs) denote physical contact sites between ER and mitochondria that mediate bidirectional communications between the two organelles. Although Ca2+ transport from ER to mitochondria is vital for mitochondrial homeostasis and energy metabolism, unrestrained Ca2+ transfer may result in mitochondrial Ca2+ overload, mitochondrial damage and cell death. Here we summarize the roles of MAMs in cell physiology and its impact in pathological conditions with a focus on cardiovascular disease. The possibility of manipulating ER-mitochondria contacts as potential therapeutic approaches is also discussed.

Automated summary

The endoplasmic reticulum (ER) and mitochondria are interconnected organelles that play vital roles in cell signaling and function. Communication between the ER and mitochondria through MAMs is crucial for regulating energy metabolism and cell fate. However, uncontrolled Ca2+ transfer can lead to mitochondrial damage and cell death. This article summarizes the roles of MAMs in cell physiology and its significance in cardiovascular disease, as well as discusses the potential of manipulating ER-mitochondria contacts as a therapeutic approach.