{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T04:08:28Z","timestamp":1788754108553,"version":"build-2803163510"},"reference-count":136,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"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. Cell Dev. Biol."],"abstract":"<jats:p>Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease with limited therapeutic options and a median survival of only 3\u20135 years. Although antifibrotic agents such as pirfenidone (PFD) and nintedanib can decelerate functional decline, they fail to reverse established fibrosis, underscoring an urgent need for novel therapeutic paradigms. Emerging evidence has positioned mitophagy\u2014the selective autophagic clearance of damaged mitochondria\u2014at the nexus of IPF pathogenesis. In this review, we systematically dissect the regulatory networks governing mitophagy, encompassing the canonical PINK1\/Parkin pathway, receptor-mediated mechanisms (BNIP3\/NIX\/FUNDC1), and their intricate cross-talk with endoplasmic reticulum stress (ERS) and ferroptosis, highlighting how these interconnected pathways converge to determine alveolar epithelial cell (AEC) fate, fibroblast activation, and inflammatory reprogramming. Notably, the pathological impact of mitophagy is highly cell-type-specific and context-dependent, exhibiting protective functions in epithelial cells while paradoxically promoting pro-fibrotic phenotypes in macrophages under certain conditions, which poses both challenges and opportunities for therapeutic intervention. Furthermore, we critically evaluate emerging pharmacological and biological strategies targeting mitophagy, and propose that future combination regimens\u2014guided by non-invasive mitophagy biomarkers\u2014may overcome current clinical bottlenecks. By integrating mechanistic insights with translational perspectives, this review provides a roadmap for developing mitophagy-targeted interventions as a next-generation therapeutic paradigm for IPF.<\/jats:p>","DOI":"10.3389\/fcell.2026.1925197","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T03:37:06Z","timestamp":1788752226000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitophagy in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic opportunities"],"prefix":"10.3389","volume":"14","author":[{"given":"Mengzhu","family":"He","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Health and Multimorbidity, Institute of Respiratory Health, State Key Laboratory of Respiratory Health and Multimorbidity, Frontiers Science Center for Disease-related Molecular Network, Sichuan Provincial Engineering Laboratory of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, West China School of Medicine, Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"Tianfu Jincheng Laboratory","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Health and Multimorbidity, Institute of Respiratory Health, State Key Laboratory of Respiratory Health and Multimorbidity, Frontiers Science Center for Disease-related Molecular Network, Sichuan Provincial Engineering Laboratory of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, West China School of Medicine, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Health and Multimorbidity, Institute of Respiratory Health, State Key Laboratory of Respiratory Health and Multimorbidity, Frontiers Science Center for Disease-related Molecular Network, Sichuan Provincial Engineering Laboratory of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, West China School of Medicine, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaotong","family":"Cong","sequence":"additional","affiliation":[{"name":"Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Health and Multimorbidity, Institute of Respiratory Health, State Key Laboratory of Respiratory Health and Multimorbidity, Frontiers Science Center for Disease-related Molecular Network, Sichuan Provincial Engineering Laboratory of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, West China School of Medicine, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1165\/rcmb.2019-0013ED","article-title":"The STATus of STAT3 in lung cell senescence?","volume":"61","author":"Adnot","year":"2019","journal-title":"Am. 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