MitoQ alleviates mitochondria damage in sepsis-acute lung injury in a citrate synthase dependent manner.

Abstract

Sepsis is a systemic inflammatory disease caused by severe infection, involving multiple organs in the body, with the lungs being the most susceptible, leading patients to develop acute lung injury (ALI). Mitoquinone Mesylate (MitoQ) is an antioxidant specifically designed to target mitochondria, and it has anti-aging and antioxidant properties. This study aimed to investigate the protective effects of MitoQ on sepsis-induced ALI and its mechanisms. C57BL/6 mice were used to establish the cecal ligation and puncture (CLP) model of sepsis and were orally administered or not administered MitoQ for two weeks. MitoQ effectively alleviated sepsis-induced lung tissue damage, inflammatory responses, oxidative stress, and apoptosis. Furthermore, MitoQ significantly inhibited oxidative stress and mitochondrial damage in pulmonary macrophages. Mechanistically, MitoQ upregulated the mRNA and protein levels of citrate synthase (CS) in lung tissues and pulmonary macrophages. Silencing the CS gene with siRNA significantly reduced the protective effects of MitoQ against oxidative stress, inflammation, and cell apoptosis. In conclusion, MitoQ alleviates sepsis-induced ALI by preserving mitochondrial function.