Impact of mitochondrial dynamics on metabolic disease and inflammation

Abstract

Mitochondria are highly dynamic organelles that frequently fuse and divide in response to cellular energy demands, differentiation or pathological conditions. In vertebrates, mitofusin-1 and -2  are involved in mitochondrial fusion while dynamin-related protein 1 (DRP1) and mitochondrial fission factor control mitochondrial fission. In our previous study, by using liver specific DRP1 knockout (Drp1LiKO) mice, we reported that mitochondrial dynamics play a protective role against metabolic disorders such as diabetes and obesity through induction of fibroblast growth factor 21. On the other hand, histological analysis revealed that Drp1LiKO liver exhibited severe inflammation and fibrosis, reminiscences of nonalcoholic steatohepatitis. In this study, the role of mitochondrial dynamics on inflammasome signaling was explored. Here, we found that NLRP3 dependent caspase-1 activation and interleukin-1 beta secretion were markedly increased in Drp1LiKO liver, possibly associated with the defective autophagic degradation and increased reactive oxygen species (ROS) generation. Thus, our results provide new insight into the role of mitochondrial dynamics in inflammasome activation.