{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:04:05Z","timestamp":1785301445078,"version":"3.55.0"},"reference-count":210,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Doxorubicin (DOX) is a broad-spectrum anthracycline chemotherapeutic agent, and its clinical application is severely limited by dose-dependent cardiotoxicity (DIC), for which there are currently no effective clinical interventions. Mitochondria are the central organelles regulating myocardial energy metabolism and cell survival, and mitochondrial dysfunction is considered the initiating and core mechanism underlying DIC. DOX disrupts the mitochondrial quality control (MQC) system and induces mitochondrial metabolic reprogramming, thereby leading to mitochondrial dysfunction. This results in excessive production of mitochondrial reactive oxygen species (mROS) and leakage of mitochondrial DNA (mtDNA), ultimately inducing PANoptosis. PANoptosis is a newly defined inflammatory programmed cell death pathway that integrates key features of apoptosis, pyroptosis, and necroptosis. This review delves into the molecular mechanisms by which mitochondrial dysfunction triggers PANoptosis in DIC, focusing on key aspects such as impaired mitochondrial protein homeostasis, mitochondrial dynamics imbalance, suppressed mitochondrial biogenesis, inhibited mitophagy, and mitochondrial metabolic reprogramming. It systematically discusses DIC-targeted intervention strategies against mitochondrial homeostasis and PANoptosis, including mitochondrial-targeted antioxidants, mitochondrial dynamics regulators, mitophagy activators, mitochondrial biogenesis promoters, mitochondrial transplantation, PANoptosis inhibitors, nanomedicine delivery systems, and gene\/cell therapy. The aim is to balance the antitumor efficacy of DOX and reduce its cardiac adverse effects, thereby providing a new theoretical basis and potential therapeutic targets for the clinical prevention and treatment of DIC.<\/jats:p>","DOI":"10.3389\/fphar.2026.1852905","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:49:06Z","timestamp":1785300546000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial dysfunction-driven PANoptosis in doxorubicin-induced cardiotoxicity: mechanistic insights and intervention strategies"],"prefix":"10.3389","volume":"17","author":[{"given":"Xinyu","family":"Xue","sequence":"first","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Graduate School, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xihan","family":"Liao","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Ji","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Graduate School, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailin","family":"Huang","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Graduate School, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanlin","family":"Wu","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.36740\/WLek202307113","article-title":"Assessment of cardioprotective effect of necrostatin-1 stable in a mice model of acute doxorubicin-induced cardiotoxicity","volume":"76","author":"Abbas","year":"2023","journal-title":"Wiad. 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