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- Title
Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice.
- Authors
Thierbach, René; Schulz, Tim J; Isken, Frank; Voigt, Anja; Mietzner, Brun; Drewes, Gunnar; von Kleist-Retzow, Jürgen-Christoph; Wiesner, Rudolf J; Magnuson, Mark A; Puccio, Hélène; Pfeiffer, Andreas F H; Steinberg, Pablo; Ristow, Michael
- 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.
- Publication
Human molecular genetics, 2005, Vol 14, Issue 24, p3857
- ISSN
0964-6906
- Publication type
Journal Article
- DOI
10.1093/hmg/ddi410