Mechanistic insights and challenges in mitochondrial regulation of macrophage polarization and inflammatory responses

Inflammation has a dual nature; excessive or uncontrolled inflammation can trigger metabolic inflammatory diseases, in which immune cells, especially macrophages, play a crucial role. Mitochondria, as the core of cellular energy metabolism, are closely related to macrophage polarization and inflammation regulation. Mitochondrial dysfunction can trigger inflammatory responses through the activation of multiple signaling pathways, involving multiple signaling pathways, including Cyclic GMP-AMP Synthase - Stimulator of Interferon Genes 1, inflammasomes, and Retinoic acid-Inducible Gene I (RIG-I). Currently, the role of mitochondria in regulating inflammatory responses is increasingly prominent; however, current research still faces many challenges, such as a lack of mechanistic connections, unclear details of key molecules, insufficiently refined experimental strategies, and difficulties in clinical translation. Future research needs to leverage advanced technologies to delve deeper into the mechanisms, improve the bioavailability and tissue-specific delivery of mitochondrial-targeted drugs, establish personalized evaluation criteria, and promote interdisciplinary innovation to facilitate the transition of mitochondrial-targeted therapy from basic research to clinical application.