Affordable Access

Publisher Website

HDMCP uncouples yeast mitochondrial respiration and alleviates steatosis in L02 and hepG2 cells by decreasing ATP and H2O2levels: A novel mechanism for NAFLD

Journal of Hepatology
Publication Date
DOI: 10.1016/j.jhep.2008.10.034
  • Hdmcp
  • Non-Alcoholic Fatty Liver Disease
  • Steatosis
  • Uncoupling Protein
  • Hepg2 Cells
  • L02 Cells
  • Biology
  • Chemistry
  • Medicine


Background/Aims To explore the uncoupling activity of hepatocelluar downregulated mitochondrial carrier protein (HDMCP) in a yeast expression system and its function in non-alcoholic fatty liver disease (NAFLD). Methods Molecular cloning and RT-PCR were used for yeast protein expression and uncoupling activity was assessed. Western blot analysis was used to determine HDMCP level in rat NAFLD and steatotic L02 and hepG2 cell models where their presence was confirmed by pathologic (Nile red and H-E staining) and biochemical changes. RNA interference was used to knock down HDMCP level and mitochondrial ATP and hydroperoxide levels were measured for potential mechanism exploration. Results We found a significant GDP insensitive uncoupling activity of HDMCP in yeast mitochondria and its increased expression in animal and cell models. HDMCP was significantly increased with culture time and steatosis was aggravated when HDMCP level was knocked down. Furthermore, we found that HDMCP might function through promoting ATP depletion and decreasing H 2O 2 production. Conclusion This study adds supportive data to the hypothesis that HDMCP might be a long postulated liver-specific uncoupling protein and broadens our understanding of the pathogenesis of NAFLD. More importantly, HDMCP might become a novel drug target for its ability in alleviating hepatic steatosis.

There are no comments yet on this publication. Be the first to share your thoughts.