Impact of Drp1 Loss on Organelle Interaction, Metabolism, and Inflammation in Mouse Liver

Dynamin-related protein 1 (Drp1) plays a critical role in mitochondrial fission and liver function. The interactions between mitochondria, endoplasmic reticulum (ER), and lipid droplets (LDs) are essential for lipid metabolism. In this study, liver-specific Drp1 knockout (Drp1LiKO) mice were utilized to investigate the impact of disrupted organelle interactions. Analysis revealed increased interactions between mitochondria and LDs, as well as among ER, mitochondria, and LDs in Drp1LiKO mice. As a result, impaired fatty acid metabolism was observed, leading to liver inflammation. In vitro studies using primary hepatocytes from Drp1LiKO mice further confirmed disrupted lipid metabolism and increased inflammation. These findings underscore the significance of Drp1 in maintaining organelle interactions for proper lipid metabolism and liver health. Tar-geting Drp1-mediated interactions may present a promising approach for the treatment of liver diseases associated with lipid metabolism dysregulation. Mice were fasted for 17 hours and then refed for 4 hours before sacrificed. Total RNA was isolated from mouse liver using TRIzol Reagent (Invitrogen Corporation, Carlsbad, CA, USA) and purified using a SV Total RNA Isolation System (Promega Corporation, Madison, WI, USA) according to the manufacturer’s instructions. Gene expression profiling was performed using the Whole Mouse Genome Microarray 4x44K v2 platform that contains 39,430 probes (Agilent Technologies).