Role of mitochondrial-associated endoplasmic reticulum membrane in myocardial ischemia-reperfusion injury

Abstract

The endoplasmic reticulum (ER) and mitochondria (MT) are two essential organelles within cells. Endoplasmic reticulum stress (ERS) and mitochondrial damage are key drivers of cell death in myocardial ischemia-reperfusion injury (MIRI), and their interplay also exerts important regulatory effects on the progression of cardiomyocyte injury. As a structural hub for physical coupling between the ER and mitochondria, mitochondria-associated endoplasmic reticulum membranes (MAMs) play a pivotal role in the pathogenesis and progression of MIRI. Disruption of MAMs’ architecture in cardiomyocytes can directly or indirectly trigger multiple pathological processes, including redox imbalance, ER stress, mitochondrial damage, energy depletion, and programmed cell death. This review first elaborates on the structural changes and functional consequences of the ER and mitochondria in MIRI, summarizes the structural features of MAMs and the regulatory functions and specific mechanisms of their enriched proteins in modulating calcium homeostasis, oxidative stress, and mitochondrial damage under MIRI pathology, and finally lists several bioactive components derived from traditional Chinese medicine that ameliorate MIRI by targeting MAMs-associated proteins.

Keywords

MAMs / calcium ion balance / mitochondrial damage / oxidative stress / myocardial ischemia-reperfusion

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