Sun L, Sun XY, Na ZH, Liu YJ, Li L, Cao TY, Li XR, Fan YD, Hu GP, Wang S. Excessive mitochondrial fission in myocardial ischemia/reperfusion injury: Pathophysiological relevance and potential cardioprotective modulation by plant-derived interventions and electroacupuncture. World J Cardiol 2026; 18(10): 125900 [DOI: 10.4330/wjc.125900]
Corresponding Author of This Article
Shuo Wang, MD, State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, West District, Tuanbo New City, Jinghai District, Tianjin 301617, China. wssean1609@163.com
Research Domain of This Article
Cardiac & Cardiovascular Systems
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review-article
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Sun L, Sun XY, Na ZH, Liu YJ, Li L, Cao TY, Li XR, Fan YD, Hu GP, Wang S. Excessive mitochondrial fission in myocardial ischemia/reperfusion injury: Pathophysiological relevance and potential cardioprotective modulation by plant-derived interventions and electroacupuncture. World J Cardiol 2026; 18(10): 125900 [DOI: 10.4330/wjc.125900]
World J Cardiol. Oct 26, 2026; 18(10): 125900 Published online Oct 26, 2026. doi: 10.4330/wjc.125900
Excessive mitochondrial fission in myocardial ischemia/reperfusion injury: Pathophysiological relevance and potential cardioprotective modulation by plant-derived interventions and electroacupuncture
Li Sun, Xing-Yi Sun, Zi-Han Na, Yi-Jia Liu, Lin Li, Tian-Yu Cao, Xin-Ran Li, Ya-Dong Fan, Gui-Ping Hu, Shuo Wang
Li Sun, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; First Teaching Hospital of Tianjin University of Traditional Chinese Medicine/National Clinical Research Center for Chinese Medicine, Tianjin 300380, China
Xing-Yi Sun, Zi-Han Na, Lin Li, Tian-Yu Cao, Xin-Ran Li, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Yi-Jia Liu, Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China
Ya-Dong Fan, School of Traditional Chinese Medicine, Faculty of Medicine, Yangzhou University, Yangzhou 225009, Jiangsu Province, China
Gui-Ping Hu, School of Engineering Medicine, Beihang University, Beijing 100191, China
Shuo Wang, State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Co-first authors: Li Sun and Xing-Yi Sun.
Co-corresponding authors: Gui-Ping Hu and Shuo Wang.
Author contributions: Sun L and Sun XY contributed to the literature search and screening, and the drafting and revision of the manuscript; Sun L contributed to the design and preparation of the figures and tables; Sun XY contributed to the extraction and curation of the data presented in the evidence tables; Na ZH contributed to the preparation of the Supplementary materials; Liu YJ, Cao TY and Li XR contributed to the cross-check of the extracted information and Supplementary materials; Li L, Hu GP, Wang S and Fan YD contributed to the funding acquisition; Fan YD and Wang S contributed to the critical revision; Hu GP contributed to the review and editing of the manuscript; Wang S contributed to the conception and supervision of the study. Hu GP and Wang S contributed equally to this work as co-corresponding authors. Sun L and Sun XY contributed equally to this work as co-first authors.
AI contribution statement: The authors declare that no AI tools were used in the development or writing of this manuscript and take full responsibility for its integrity, accuracy, and originality.
Supported by the National Natural Science Foundation of China, No. 82104565 and No. 82405328; the Research Project of the Tianjin Municipal Education Commission, No. 2023KJ144; the Young Scholar Fund Project of the State Key Laboratory of Component-Based Chinese Medicine, No. QMJJ202403; and the Open Research Project of the State Key Laboratory of Component-Based Chinese Medicine, No. CBCM2024202.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Shuo Wang, MD, State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, West District, Tuanbo New City, Jinghai District, Tianjin 301617, China. wssean1609@163.com
Received: July 21, 2026 Revised: September 9, 2026 Accepted: October 20, 2026 Published online: October 26, 2026 Processing time: 94 Days and 22.2 Hours
Abstract
Myocardial ischemia/reperfusion injury (MI/RI) remains an unresolved problem despite reperfusion therapies, including percutaneous coronary intervention. Mitochondria are central mediators of reperfusion-associated cardiomyocyte injury, with excessive fission implicated as a potentially important mechanism linking acute metabolic stress to fragmentation, bioenergetic failure, and cell death. Reactive oxygen species, Ca2+ overload, mitochondrial permeability transition pore opening and membrane-potential loss promote dynamin-related protein 1-centered (Drp1-centered) fission, often involving mitochondrial fission factor, mitochondrial fission 1 protein and site-specific Drp1 phosphorylation. By disrupting mitochondrial networks and oxidative phosphorylation, this process contributes to cytochrome c release, apoptosis, microvascular dysfunction and impaired recovery. Impaired mitofusin 1/2-mediated and optic atrophy 1-mediated fusion limits repair and quality control, supporting investigation of this fission-dominant imbalance as a target for cardioprotection. Preclinical studies suggest plant-derived natural products, multi-component botanical preparations and electroacupuncture may influence this imbalance. Reported effects include attenuated Drp1 signaling, altered fusion-protein expression, preserved membrane potential, inhibited permeability transition, reduced oxidative stress and apoptosis, and modulated upstream metabolic/stress-responsive pathways. However, hypoxia/reoxygenation, oxygen-glucose deprivation/reoxygenation, non-reperfused ischemia/infarction and stress models provide surrogate or supportive evidence rather than direct evidence of MI/RI. Heterogeneity in models, timing, dosage, readouts, causal validation and botanical quality control limits interpretation. This review examines these mechanisms, interventions and translational priorities. Clinical efficacy and safety of these interventions in MI/RI have not been established.
Core Tip: Excessive mitochondrial fission is not merely a morphological consequence of myocardial ischemia/reperfusion injury, but a potential amplifier of mitochondrial dysfunction and cardiomyocyte death. This review highlights the complementary contributions of dynamin-related protein 1-centered fission activation and impaired fusion-mediated network repair. It further emphasizes that broad mitochondrial protection should not be equated with direct modulation of the fusion-fission machinery. Plant-derived interventions and electroacupuncture show experimental promise, but mechanistic causality and translational relevance remain insufficiently established.
