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Review
. 2024 Apr 17:15:1398381.
doi: 10.3389/fphar.2024.1398381. eCollection 2024.

Mitochondria-associated endoplasmic reticulum membranes as a therapeutic target for cardiovascular diseases

Yanqiu Ding #  1   2 , Nanyang Liu #  3 , Dawu Zhang  1   4 , Lijun Guo  1 , Qinghua Shang  1 , Yicheng Liu  1 , Gaocan Ren  1 , Xiaochang Ma  1   4
Affiliations
Review

Mitochondria-associated endoplasmic reticulum membranes as a therapeutic target for cardiovascular diseases

Yanqiu Ding et al. Front Pharmacol. .

Abstract

Cardiovascular diseases (CVDs) are currently the leading cause of death worldwide. In 2022, the CVDs contributed to 19.8 million deaths globally, accounting for one-third of all global deaths. With an aging population and changing lifestyles, CVDs pose a major threat to human health. Mitochondria-associated endoplasmic reticulum membranes (MAMs) are communication platforms between cellular organelles and regulate cellular physiological functions, including apoptosis, autophagy, and programmed necrosis. Further research has shown that MAMs play a critical role in the pathogenesis of CVDs, including myocardial ischemia and reperfusion injury, heart failure, pulmonary hypertension, and coronary atherosclerosis. This suggests that MAMs could be an important therapeutic target for managing CVDs. The goal of this study is to summarize the protein complex of MAMs, discuss its role in the pathological mechanisms of CVDs in terms of its functions such as Ca2+ transport, apoptotic signaling, and lipid metabolism, and suggest the possibility of MAMs as a potential therapeutic approach.

Keywords: cardiovascular diseases; coronary atherosclerosis; mitochondria-associated endoplasmic reticulum membrane; myocardial ischemia; therapeutic target.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
MAMs are regions where the OMM and certain areas of the ER membrane overlap without membrane fusion, which enables communication between organelles and bi-directionally regulates cellular functions through connectivity proteins. The major protein complexes on MAMs include IP3R1-GRP75-VDAC1, BAP31-Fis1, VAPB-PTPIP51, MFN2-MFN1/2, etc. The main functions of MAMs include Ca2+ signaling, synthesis and transfer of lipids, mitochondrial dynamics, autophagy, apoptosis, oxidative stress, etc. MAMs are crucial in developing CVDs, including myocardial infarction, myocardial I/R injury, diabetic cardiomyopathy, etc. At the same time, MAMs have also become the target of drug therapy for CVDs.
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Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. National Natural Science Foundation of China Project (82374280); National Natural Science Foundation of China Youth Science Fund Project (82104677).