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

Yiping Han; Lin Zhao; Pengshuo Lou; Chen Wang; Mingxin Yuan; Yingli Yu; Yiping Han; Lin Zhao; Pengshuo Lou; Chen Wang; Mingxin Yuan; Yingli Yu

doi:10.3934/biophy.2026016

AIMS Biophysics

2026, Volume 13, Issue 3: 255-286. doi: 10.3934/biophy.2026016

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Review

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

1.
Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
2.
Center of Drug Safety Evaluation, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
3.
Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang 050000, China
4.
State Key Laboratory of Component-based Chinese Medicine, Tianjin 301617, China

Received: 01 May 2026 Revised: 02 July 2026 Accepted: 13 July 2026 Published: 27 July 2026

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.
- MAMs,
- calcium ion balance,
- mitochondrial damage,
- oxidative stress,
- myocardial ischemia-reperfusion
Citation: Yiping Han, Lin Zhao, Pengshuo Lou, Chen Wang, Mingxin Yuan, Yingli Yu. Role of mitochondrial-associated endoplasmic reticulum membrane in myocardial ischemia-reperfusion injury[J]. AIMS Biophysics, 2026, 13(3): 255-286. doi: 10.3934/biophy.2026016

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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.

Acknowledgments

This work was supported by the National Natural Science Foundation of China under Grant No. 82204669.

Conflict of interest

The authors declare that they have no conflict of interest.

Author contributions

Author Yiping Han: Investigation (literature search and screening), Writing – original draft, Visualization. Author Lin Zhao: Investigation (data extraction and synthesis), Writing – original draft. Author Pengshuo Lou: Investigation (validation of extracted data), Visualization (graphical abstract), Writing – review & editing. Author Chen Wang: Writing – review & editing. Author Mingxin Yuan: Writing – review & editing. Corresponding author Yingli Yu: Conceptualization, Supervision, Writing – review & editing, Funding acquisition, Project administration. All authors have read and approved the final version of the manuscript for publication.

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