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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| Format: | Article |
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Frontiers Media S.A.
2025-06-01
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| 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. |
| format | Article |
| id | doaj-art-7f01b8528b104f8195abe61ce32f63ef |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| 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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