Dexmedetomidine alleviates LPS-induced apoptosis and inflammation in macrophages by eliminating damaged mitochondria via PINK1 mediated mitophagy.

The macrophage is an innate immune response cell that plays an important role in the development of sepsis. Dexmedetomidine (DEX) is a sedation drug, which have anti-oxidative, anti-inflammatory and anti-apoptosis effects and can be used on sepsis patients in the ICU. However, its mechanisms of action remain poorly understood. PTEN-induced putative kinase 1 (PINK1) is a mitochondrial serine/threonine protein kinase that recognizes damaged mitochondria and leads to mitophagy. This study investigated the effects of DEX on Lipopolysaccharides(LPS)-induced macrophage injury and explained the underlying mechanisms. The results showed that LPS treatment caused mitochondrial damage, mitochondria-dependent apoptosis and PINK1-mediated mitophagy; at the same time, PINK1 has a protective effect on LPS-induced macrophage apoptosis and inflammation by mitophagy that eliminates dysfunctional mitochondria. DEX could promote the clearance of damaged mitochondria characterized by low Mitochondrial membrane potential (MMP) and high reactive oxygen species(ROS), thus exerting a protective effect in LPS treated macrophages, and PINK1 mediated mitophagy is required for this protective effect.