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

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          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 Ca 2+ transport, apoptotic signaling, and lipid metabolism, and suggest the possibility of MAMs as a potential therapeutic approach.

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          Most cited references131

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          2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

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            Mitochondrial fission, fusion, and stress.

            Mitochondrial fission and fusion play critical roles in maintaining functional mitochondria when cells experience metabolic or environmental stresses. Fusion helps mitigate stress by mixing the contents of partially damaged mitochondria as a form of complementation. Fission is needed to create new mitochondria, but it also contributes to quality control by enabling the removal of damaged mitochondria and can facilitate apoptosis during high levels of cellular stress. Disruptions in these processes affect normal development, and they have been implicated in neurodegenerative diseases, such as Parkinson's.
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              Mitochondria supply membranes for autophagosome biogenesis during starvation.

              Starvation-induced autophagosomes engulf cytosol and/or organelles and deliver them to lysosomes for degradation, thereby resupplying depleted nutrients. Despite advances in understanding the molecular basis of this process, the membrane origin of autophagosomes remains unclear. Here, we demonstrate that, in starved cells, the outer membrane of mitochondria participates in autophagosome biogenesis. The early autophagosomal marker, Atg5, transiently localizes to punctae on mitochondria, followed by the late autophagosomal marker, LC3. The tail-anchor of an outer mitochondrial membrane protein also labels autophagosomes and is sufficient to deliver another outer mitochondrial membrane protein, Fis1, to autophagosomes. The fluorescent lipid NBD-PS (converted to NBD-phosphotidylethanolamine in mitochondria) transfers from mitochondria to autophagosomes. Photobleaching reveals membranes of mitochondria and autophagosomes are transiently shared. Disruption of mitochondria/ER connections by mitofusin2 depletion dramatically impairs starvation-induced autophagy. Mitochondria thus play a central role in starvation-induced autophagy, contributing membrane to autophagosomes. Copyright (c) 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2348399/overviewRole: Role:
                URI : https://loop.frontiersin.org/people/1286717/overviewRole: Role:
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                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                17 April 2024
                2024
                : 15
                : 1398381
                Affiliations
                [1] 1 Cardiovascular Department , Xiyuan Hospital , China Academy of Chinese Medical Sciences , Beijing, China
                [2] 2 Graduate School , Beijing University of Chinese Medicine , Beijing, China
                [3] 3 Department of Geratology , Xiyuan Hospital , China Academy of Chinese Medical Sciences , Beijing, China
                [4] 4 State Key Laboratory of Traditional Chinese Medicine Syndrome , Xiyuan Hospital , China Academy of Chinese Medical Sciences , Beijing, China
                Author notes

                Edited by: Yuxiang Dong, University of Nebraska Medical Center, United States

                Reviewed by: Derek Leas, University of Florida, United States

                Wangbin Wu, University of Nebraska Medical Center, United States

                *Correspondence: Xiaochang Ma, maxiaochang1118@ 123456163.com
                [ † ]

                These authors have contributed equally to this work

                Article
                1398381
                10.3389/fphar.2024.1398381
                11061472
                38694924
                21b6dc37-f0ef-4933-8e17-0dc0ed09b87a
                Copyright © 2024 Ding, Liu, Zhang, Guo, Shang, Liu, Ren and Ma.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 March 2024
                : 05 April 2024
                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).
                Categories
                Pharmacology
                Review
                Custom metadata
                Experimental Pharmacology and Drug Discovery

                Pharmacology & Pharmaceutical medicine
                cardiovascular diseases,mitochondria-associated endoplasmic reticulum membrane,therapeutic target,coronary atherosclerosis,myocardial ischemia

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