{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:51:22Z","timestamp":1792133482172,"version":"4.4.0"},"reference-count":125,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,25]],"date-time":"2024-02-25T00:00:00Z","timestamp":1708819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health (Ricerca Corrente)","award":["2022E75TWB"],"award-info":[{"award-number":["2022E75TWB"]}]},{"name":"Italian Ministry of Health (Ricerca Corrente)","award":["CUP B53C22004000006"],"award-info":[{"award-number":["CUP B53C22004000006"]}]},{"name":"European Union-NextGenerationEU","award":["2022E75TWB"],"award-info":[{"award-number":["2022E75TWB"]}]},{"name":"European Union-NextGenerationEU","award":["CUP B53C22004000006"],"award-info":[{"award-number":["CUP B53C22004000006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitochondrial dysfunction, a feature of heart failure, leads to a progressive decline in bioenergetic reserve capacity, consisting in a shift of energy production from mitochondrial fatty acid oxidation to glycolytic pathways. This adaptive process of cardiomyocytes does not represent an effective strategy to increase the energy supply and to restore the energy homeostasis in heart failure, thus contributing to a vicious circle and to disease progression. The increased oxidative stress causes cardiomyocyte apoptosis, dysregulation of calcium homeostasis, damage of proteins and lipids, leakage of mitochondrial DNA, and inflammatory responses, finally stimulating different signaling pathways which lead to cardiac remodeling and failure. Furthermore, the parallel neurohormonal dysregulation with angiotensin II, endothelin-1, and sympatho-adrenergic overactivation, which occurs in heart failure, stimulates ventricular cardiomyocyte hypertrophy and aggravates the cellular damage. In this review, we will discuss the pathophysiological mechanisms related to mitochondrial dysfunction, which are mainly dependent on increased oxidative stress and perturbation of the dynamics of membrane potential and are associated with heart failure development and progression. We will also provide an overview of the potential implication of mitochondria as an attractive therapeutic target in the management and recovery process in heart failure.<\/jats:p>","DOI":"10.3390\/ijms25052667","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T06:50:23Z","timestamp":1708930223000},"page":"2667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":120,"title":["Mitochondrial Dysfunction in Heart Failure: From Pathophysiological Mechanisms to Therapeutic Opportunities"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4845-117X","authenticated-orcid":false,"given":"Giovanna","family":"Gallo","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, Via di Grottarossa 1035-1039, 00189 Rome, RM, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9808-7970","authenticated-orcid":false,"given":"Speranza","family":"Rubattu","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, Via di Grottarossa 1035-1039, 00189 Rome, RM, Italy"},{"name":"IRCCS Neuromed, 86077 Pozzilli, IS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Volpe","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Roma, 00166 Rome, RM, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1161\/01.RES.56.3.377","article-title":"Ultrastructural morphometric analysis of myocardium from dogs, rats, hamsters, mice, and from human hearts","volume":"56","author":"Schaper","year":"1985","journal-title":"Circ. 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