Fig. 5.

Mitochondria-based therapeutic interventions. Mitochondria-targeted antioxidants such as MitoQ, MitoVitE, and MitoTempol are selectively targeted to mitochondria by conjugating to a lipophilic cation decyl-triphenylphosphonium (TPP⁺). The positive charge of cation enables the molecules to accumulate in mitochondrial matrix, therefore, specifically quench the mitochondrial ROS. Non-antioxidants Urolithin A, Mdivi-1, and Cyclosporin A improve mitochondrial quality by promoting mitophagy, inhibiting mitochondrial fission, and blocking MPTP, respectively. Metformin plays multiple roles on mitochondria, including enhancing mitophagy, reducing mtROS, preventing ox-mtDNA production, and inhibiting mitochondrial protein translation. These compounds target different aspects of mitochondria and exhibit great potential in reducing sepsis-induced mitochondrial damage, excessive inflammation, and organ dysfunction