Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice.
Authors: Thierbach R; Schulz TJ; Isken F; Voigt A; Mietzner B; Drewes G; von Kleist-Retzow JC; Wiesner RJ; Magnuson MA; Puccio H; Pfeiffer AF; Steinberg P; Ristow M Year: 2005 Journal: Human molecular genetics Abstract: We have disrupted expression of the mitochondrial Friedreich ataxia protein frataxin specifically in murine hepatocytes to generate mice with impaired mitochondrial function and decreased oxidative phosphorylation. These animals have a reduced life span and develop multiple hepatic tumors. Livers also show increased oxidative stress, impaired respiration and reduced ATP levels paralleled by reduced activity of iron-sulfur cluster (Fe/S) containing proteins (ISP), which all leads to increased hepatocyte turnover by promoting both apoptosis and proliferation. Accordingly, phosphorylation of the stress-inducible p38 MAP kinase was found to be specifically impaired following disruption of frataxin. Taken together, these findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals. Reference
Integration:
Created on Jan. 3, 2013, 6:41 p.m. Not linked Integrated: False
Comment on This Data Unit