Mitochondria orchestrated immune microenvironment and response in health and disease-clinically relevant outlook and recommendations

The review highlights that immune cell function relies on cell-type-specific mitochondrial metabolism, alongside the balance of mitochondrial dynamics and mitophagy. Furthermore, IMT and extracellular vesicle (EV)-mediated mtDAMPs signaling form a crucial intercellular communication network that regulates the energy metabolism and immune phenotype of recipient cells. Across various diseases, mitochondrial-immune remodeling points to three conserved checkpoints, providing universal therapeutic targets. Driven by breakthroughs in single-cell sequencing and multi-omics analysis, the decoding of mitochondrial heterogeneity has facilitated a paradigm shift from reactive to predictive and proactive medicine. Finally, this review integrates extensive studies on mitochondria-targeted therapeutic strategies, providing highly translatable avenues for personalized immunotherapy.