A Clinical Bioenergetics Framework for Vitiligo: From Mitochondrial Stress and mtDNA-Mediated Immune Activation to Biomarker-Guided Phenotyping

Vitiligo is an acquired depigmenting disorder in which melanocyte loss has traditionally been interpreted through an autoimmune lens. However, immune activation alone does not fully explain why melanocytes become selectively vulnerable, why oxidative stress is frequently detected in association with depigmentation, or why some patient subgroups exhibit systemic metabolic abnormalities. This narrative review provides a targeted synthesis of current mechanistic, translational, and clinical evidence to propose a clinical bioenergetics framework for vitiligo. We integrate findings supporting a convergence model in which mitochondrial stress, redox imbalance, mitochondrial DNA (mtDNA) release, innate immune sensing, adaptive cytotoxicity, and systemic metabolic context act as interconnected processes rather than independent pathways. Particular emphasis is placed on mtDNA-mediated immune activation through cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS–STING) signaling as a plausible mechanistic link between oxidative damage and autoimmune amplification. We further discuss candidate biomarker domains including oxidative stress, antioxidant defense, mitochondrial integrity, mtDNA-related variables, immune mediators, and metabolic indices and examine how their combined assessment could support biomarker-guided phenotyping, patient stratification, metabolic surveillance, and the design of precision-oriented therapeutic studies. Mitochondrial dysfunction is not presented as a universal cause of vitiligo, but as a disease-amplifying interface that offers a clinically relevant framework for understanding disease heterogeneity and guiding future translational research.