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This comprehensive review synthesizes recent evidence to elucidate mechanisms, including compromised bioenergetics, excessive reactive oxygen species (ROS), mitochondrial DNA (mtDNA) damage, and aberrant mitochondrial dynamics. Distinct from prior work, this analysis uncovers novel findings: mtDNA acts as a damage\u2010associated molecular pattern, activating cyclic GMP\u2010AMP synthase\u2013stimulator of interferon genes (cGAS\u2010STING) pathways to drive type I interferon in vitiligo and IL\u201017A in psoriasis; succinate\u2010mediated immune\u2010metabolic signaling amplifies type 2 inflammation in atopic dermatitis; and subclinical mitochondrial impairments in non\u2010lesional skin serve as early indicators of disease susceptibility across these conditions. Preclinical studies have shown that emerging therapies, including antioxidants (e.g., NMN), mitochondrial modulators (e.g., SS31), senotherapeutics, and mitochondrial transplantation, are promising strategies for restoring cellular function. Future research should focus on multi\u2010omics to dissect mitochondrial\u2010epigenetic interactions, validate mitochondrial metabolites like succinate as diagnostic biomarkers, and explore synergistic combination therapies. This integrative framework of mitochondrial\u2010driven pathology provides fresh perspectives to advance diagnostic and therapeutic innovation in dermatology.<\/jats:p>","DOI":"10.1002\/ddr.70221","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T04:46:17Z","timestamp":1767933977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mitochondrial Dysfunction in Inflammatory Skin Diseases: Mechanisms, Biomarkers, and Emerging Therapeutic Strategies"],"prefix":"10.1002","volume":"87","author":[{"given":"Mei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Dermatology Zibo Central Hospital Zibo Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Dermatology Zibo Central Hospital Zibo Shandong 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