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Med."],"abstract":"<jats:p>Heart failure (HF) is a clinical syndrome resulting from structural or functional cardiac abnormalities and represents a growing global public health challenge. Common etiologies include myocardial infarction, cardiomyopathy, and myocarditis. Mitochondrial dysfunction is now recognized as a central event in the initiation and progression of HF, making this pathogenesis a key focus of recent research. Recent studies have confirmed that HF with reduced ejection fraction (HFrEF) is driven by defects in excitation\u2013contraction coupling, leading to mechano-energetic uncoupling. In contrast, HF with preserved ejection fraction (HFpEF) is characterized by an imbalance between cardiac workload and mitochondrial energy supply. Mitochondrial dysfunction is evident in both forms of HF, with metabolic disturbances serving as both biomarkers and drivers of disease progression. However, key knowledge gaps remain, including uncertainty regarding the regulation of mitochondrial networks and the limited clinical translation of targeted therapies. Thus, the precise modulation of mitochondrial quality control and the correction of metabolic and oxidative imbalances may offer a promising approach for overcoming current therapeutic limitations. This review analyzes the current literature to summarize the pathological mechanisms and therapeutic strategies targeting mitochondrial dysfunction in HF, as a deeper understanding of these mechanisms may support the development of individualized treatment strategies for HF.<\/jats:p>","DOI":"10.31083\/rcm51920","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:17:46Z","timestamp":1788437866000},"source":"Crossref","is-referenced-by-count":0,"title":["Pathological Mechanisms and Therapeutic Potential of Mitochondrial Dysfunction in Heart Failure"],"prefix":"10.31083","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2987-0425","authenticated-orcid":true,"given":"Shige","family":"San","sequence":"first","affiliation":[{"name":"Department of Central Laboratory, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, 441021 Xiangyang, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7662-3308","authenticated-orcid":true,"given":"Xi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Affiliated Hospital of Xiangyang Vocational and Technical University, 441050 Xiangyang, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6688-959X","authenticated-orcid":true,"given":"Liang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, 441021 Xiangyang, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4478-2553","authenticated-orcid":true,"given":"Kun","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, 441021 Xiangyang, Hubei, China"},{"name":"Hubei Key Laboratory of Gynecologic Oncology and Reproductive Health, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, 441021 Xiangyang, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Valente V, Laborante R, Abdin A, Becher PM, Lainscak M, Polovina M, et al. 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