Mitochondria as immunometabolic hubs in psoriasis: pathogenic mechanisms and therapeutic prospects

Abstract

Psoriasis is a chronic, immune-mediated inflammatory dermatosis characterized by a profound dysregulation of immune-epithelial crosstalk. Beyond canonical ATP production, mitochondria function as essential intracellular immunometabolic hubs embedded within the cytokine-driven network of psoriatic lesions. Within this inflammatory niche, keratinocytes and immune cells undergo structural and metabolic adaptations. Aberrant mitochondrial stress byproducts—including mitochondrial reactive oxygen species (mtROS), oxidized mitochondrial DNA (mtDNA), and metabolic intermediates—act as secondary amplifiers that reinforce innate immune sensing and adaptive T cell responses, thereby sustaining a localized inflammatory loop. Here, we propose that targeting mitochondrial pathways provides a novel, stage-dependent therapeutic framework: stabilizing mitochondrial dynamics during acute flare-ups to halt inflammation, disrupting tissue-resident memory T (T RM ) cell metabolic fitness during the stable phase to avert relapse, and restoring regulatory T (Treg) cell oxidative phosphorylation (OXPHOS) during regression to re-establish peripheral immune tolerance. Transitioning from broad immunosuppression to precision mitochondrial modulation offers a promising paradigm for cell-specific psoriasis interventions.