The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targets

The dynamic interactions among organelles play a crucial role in facilitating various intercellular functions, with the interaction between the endoplasmic reticulum (ER) and mitochondria being acknowledged as a prominent example of an interorganellar system. Numerous studies have established that t...

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Main Authors: Jin Zhang, Dan Li, Lingjie Zhou, Yanying Li, Qian Xi, Liuyun Zhang, Juan Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1629568/full
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author Jin Zhang
Jin Zhang
Dan Li
Lingjie Zhou
Lingjie Zhou
Yanying Li
Yanying Li
Qian Xi
Liuyun Zhang
Juan Zhang
author_facet Jin Zhang
Jin Zhang
Dan Li
Lingjie Zhou
Lingjie Zhou
Yanying Li
Yanying Li
Qian Xi
Liuyun Zhang
Juan Zhang
author_sort Jin Zhang
collection DOAJ
description The dynamic interactions among organelles play a crucial role in facilitating various intercellular functions, with the interaction between the endoplasmic reticulum (ER) and mitochondria being acknowledged as a prominent example of an interorganellar system. Numerous studies have established that the majority of proteins located at the physically tethered regions between the mitochondria and ER, referred to as mitochondria-associated ER membranes (MAMs), play a crucial role in intracellular physiological processes. MAMs are dynamic membrane coupling regions arising from the interaction between the ER and the outer mitochondrial membrane (OMM). MAMs regulate many biological processes, such as Ca2+ transport, lipid metabolism, and mitochondrial dynamics. A recent study has demonstrated that the proteins associated with MAMs are crucial for both the structural integrity and functional capabilities of the MAMs. Dysregulations in the MAMs proteins are implicated in the onset and progression of various associated diseases, including cancer, neurodegenerative disorders, diabetes mellitus, and cardiovascular diseases. In this review, we provide a comprehensive overview of the protein complex associated with MAMs. We examine its involvement in the pathological mechanisms underlying these diseases, focusing on its functional roles. Additionally, we evaluate and consider the potential of MAMs as therapeutic targets for these diseases.
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spelling doaj-art-7f01b8528b104f8195abe61ce32f63ef2025-08-20T03:24:52ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-06-011310.3389/fcell.2025.16295681629568The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targetsJin Zhang0Jin Zhang1Dan Li2Lingjie Zhou3Lingjie Zhou4Yanying Li5Yanying Li6Qian Xi7Liuyun Zhang8Juan Zhang9School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, ChinaDepartment of Laboratory Medicine, Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, ChinaSchool of Laboratory Medicine, Chengdu Medical College, Chengdu, ChinaSchool of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, ChinaDepartment of Laboratory Medicine, Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, ChinaSchool of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, ChinaDepartment of Laboratory Medicine, Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, ChinaDepartment of Laboratory Medicine, Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, ChinaDepartment of Laboratory Medicine, Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, ChinaDepartment of Laboratory Medicine, Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, ChinaThe dynamic interactions among organelles play a crucial role in facilitating various intercellular functions, with the interaction between the endoplasmic reticulum (ER) and mitochondria being acknowledged as a prominent example of an interorganellar system. Numerous studies have established that the majority of proteins located at the physically tethered regions between the mitochondria and ER, referred to as mitochondria-associated ER membranes (MAMs), play a crucial role in intracellular physiological processes. MAMs are dynamic membrane coupling regions arising from the interaction between the ER and the outer mitochondrial membrane (OMM). MAMs regulate many biological processes, such as Ca2+ transport, lipid metabolism, and mitochondrial dynamics. A recent study has demonstrated that the proteins associated with MAMs are crucial for both the structural integrity and functional capabilities of the MAMs. Dysregulations in the MAMs proteins are implicated in the onset and progression of various associated diseases, including cancer, neurodegenerative disorders, diabetes mellitus, and cardiovascular diseases. In this review, we provide a comprehensive overview of the protein complex associated with MAMs. We examine its involvement in the pathological mechanisms underlying these diseases, focusing on its functional roles. Additionally, we evaluate and consider the potential of MAMs as therapeutic targets for these diseases.https://www.frontiersin.org/articles/10.3389/fcell.2025.1629568/fullmitochondria-associated ER membranesmitochondriaendoplasmic reticulumcancerneurodegenerationdiabetes mellitus
spellingShingle Jin Zhang
Jin Zhang
Dan Li
Lingjie Zhou
Lingjie Zhou
Yanying Li
Yanying Li
Qian Xi
Liuyun Zhang
Juan Zhang
The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targets
Frontiers in Cell and Developmental Biology
mitochondria-associated ER membranes
mitochondria
endoplasmic reticulum
cancer
neurodegeneration
diabetes mellitus
title The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targets
title_full The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targets
title_fullStr The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targets
title_full_unstemmed The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targets
title_short The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targets
title_sort role of mitochondria associated er membranes in disease pathology protein complex and therapeutic targets
topic mitochondria-associated ER membranes
mitochondria
endoplasmic reticulum
cancer
neurodegeneration
diabetes mellitus
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1629568/full
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