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.
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Created on Jan. 3, 2013, 6:41 p.m.
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Species: House mouse

Experiments: 0
Interventions:

Fxn disruption

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