TY  - JOUR
A1  - Thierbach, Renè
A1  - Schulz, Tim Julius
A1  - Isken, Frank
A1  - Voigt, Aanja
A1  - Mietzner, Brun
A1  - Drewes, Gunnar
A1  - von Kleist-Retzow, Jürgen-Christoph
A1  - Wiesner, Rudolf J.
A1  - Magnuson, Mark A.
A1  - Puccio, Helene
A1  - Pfeiffer, Andreas F. H.
A1  - Steinberg, Pablo
A1  - Ristow, Michael
T1  - Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice
N2  - 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
Y1  - 2005
ER  -