TY  - JOUR
A1  - Schulz, Tim Julius
A1  - Thierbach, Renè
A1  - Voigt, Anja
A1  - Drewes, Gunnar
A1  - Mietzner, Brun
A1  - Steinberg, Pablo
A1  - Pfeiffer, Andreas F. H.
A1  - Ristow, Michael
T1  - Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth : Otto Warburg revisited
N2  - More than 80 years ago Otto Warburg suggested that cancer might be caused by a decrease in mitochondrial energy metabolism paralleled by an increase in glycolytic flux. In later years, it was shown that cancer cells exhibit multiple alterations in mitochondrial content, structure, function, and activity. We have stably overexpressed the Friedreich ataxia-associated protein frataxin in several colon cancer cell lines. These cells have increased oxidative metabolism, as shown by concurrent increases in aconitase activity, mitochondrial membrane potential, cellular respiration, and ATP content. Consistent with Warburg's hypothesis, we found that frataxin-overexpressing cells also have decreased growth rates and increased population doubling times, show inhibited colony formation capacity in soft agar assays, and exhibit a reduced capacity for tumor formation when injected into nude mice. Furthermore, overexpression of frataxin leads to an increased phosphorylation of the tumor suppressor p38 mitogen-activated protein kinase, as well as decreased phosphorylation of extracellular signal-regulated kinase. Taken together, these results support the view that an increase in oxidative metabolism induced by mitochondrial frataxin may inhibit cancer growth in mammals
Y1  - 2006
UR  - http://www.jbc.org/content/281/2/977.full.pdf+html
U6  - https://doi.org/10.1074/jbc.M511064200
ER  - 
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  -