Renè Thierbach, Tim Julius Schulz, Frank Isken, Aanja Voigt, Brun Mietzner, Gunnar Drewes, Jürgen-Christoph von Kleist-Retzow, Rudolf J. Wiesner, Mark A. Magnuson, Helene Puccio, Andreas F. H. Pfeiffer, Pablo Steinberg, Michael Ristow

• 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