Difference between revisions of "Yang 2010 Cancer Biol Ther"
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{{Publication | {{Publication | ||
|title=Yang D, Wang MT, Tang Y, Chen Y, Jiang H, Jones TT, Rao K, Brewer GJ, Singh KK, Nie D (2010) Impairment of mitochondrial respiration in mouse fibroblasts by oncogenic H-RAS(Q61L). Canc Biol Ther 9:122-33. | |title=Yang D, Wang MT, Tang Y, Chen Y, Jiang H, Jones TT, Rao K, Brewer GJ, Singh KK, Nie D (2010) Impairment of mitochondrial respiration in mouse fibroblasts by oncogenic H-RAS(Q61L). Canc Biol Ther 9:122-33. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/19923925 PMID: | |info=[http://www.ncbi.nlm.nih.gov/pubmed/19923925 PMID: 19923925 Open Access] | ||
|authors=Yang D, Wang MT, Tang Y, Chen Y, Jiang H, Jones TT, Rao K, Brewer GJ, Singh KK, Nie D | |authors=Yang D, Wang MT, Tang Y, Chen Y, Jiang H, Jones TT, Rao K, Brewer GJ, Singh KK, Nie D | ||
|year=2010 | |year=2010 | ||
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|abstract=A common metabolic change in cancer is the acquisition of glycolytic phenotypes. Increased expression of glycolytic enzymes is considered as one contributing factor. The role of mitochondrial defects in acquisition of glycolytic phenotypes has been postulated but remains controversial. Here we show that functional defects in mitochondrial respiration could be induced by oncogenic H-Ras<sup>Q61L</sup> transformation, even though the mitochondrial contents or mass was not reduced in the transformed cells. First, mitochondrial respiration, as measured by mitochondrial oxygen consumption, was suppressed in NIH-3T3 cells transformed with H-Ras<sup>Q61L</sup>. Second, oligomycin or rotenone did not reduce the cellular ATP levels in the H-RasQ61L transformed cells, suggesting a diminished role of mitochondrial respiration in the cellular energy metabolism. Third, inhibition of glycolysis with iodoacetic acid reduced ATP levels at a much faster rate in H-Ras<sup>Q61L</sup> transformed cells than in the vector control cells. The reduction of cellular ATP levels was reversed by exogenously added pyruvate in the vector control cells but not in H-RasQ61L transformed cells. Finally when compared to the HRas<sup>Q61L</sup> transformed cells, the vector control cells had increased resistance toward glucose deprivation. The increased resistance was dependent on mitochondrial oxidative phosphorylation since rotenone or oligomycin abolished the increased survival of the vector control cells under glucose deprivation. The results also suggest an inability of the H-RasQ61L transformed cells to reactivate mitochondrial respiration under glucose deprivation. Taken together, the data suggest that mitochondrial respiration can be impaired during transformation of NIH-3T3 cells by oncogeneic H-Ras<sup>Q61L</sup>. | |abstract=A common metabolic change in cancer is the acquisition of glycolytic phenotypes. Increased expression of glycolytic enzymes is considered as one contributing factor. The role of mitochondrial defects in acquisition of glycolytic phenotypes has been postulated but remains controversial. Here we show that functional defects in mitochondrial respiration could be induced by oncogenic H-Ras<sup>Q61L</sup> transformation, even though the mitochondrial contents or mass was not reduced in the transformed cells. First, mitochondrial respiration, as measured by mitochondrial oxygen consumption, was suppressed in NIH-3T3 cells transformed with H-Ras<sup>Q61L</sup>. Second, oligomycin or rotenone did not reduce the cellular ATP levels in the H-RasQ61L transformed cells, suggesting a diminished role of mitochondrial respiration in the cellular energy metabolism. Third, inhibition of glycolysis with iodoacetic acid reduced ATP levels at a much faster rate in H-Ras<sup>Q61L</sup> transformed cells than in the vector control cells. The reduction of cellular ATP levels was reversed by exogenously added pyruvate in the vector control cells but not in H-RasQ61L transformed cells. Finally when compared to the HRas<sup>Q61L</sup> transformed cells, the vector control cells had increased resistance toward glucose deprivation. The increased resistance was dependent on mitochondrial oxidative phosphorylation since rotenone or oligomycin abolished the increased survival of the vector control cells under glucose deprivation. The results also suggest an inability of the H-RasQ61L transformed cells to reactivate mitochondrial respiration under glucose deprivation. Taken together, the data suggest that mitochondrial respiration can be impaired during transformation of NIH-3T3 cells by oncogeneic H-Ras<sup>Q61L</sup>. | ||
|keywords=Ras, Mitochondrial respiration, Glycolysis, Electron transport chain, Complex IV, Transformation, Cellular energy metabolism, ATP | |keywords=Ras, Mitochondrial respiration, Glycolysis, Electron transport chain, Complex IV, Transformation, Cellular energy metabolism, ATP | ||
|mipnetlab= | |mipnetlab=US IL Springfield Brewer GJ | ||
|discipline=Biomedicine | |discipline=Biomedicine | ||
}} | }} | ||
Revision as of 16:53, 19 March 2015
| Yang D, Wang MT, Tang Y, Chen Y, Jiang H, Jones TT, Rao K, Brewer GJ, Singh KK, Nie D (2010) Impairment of mitochondrial respiration in mouse fibroblasts by oncogenic H-RAS(Q61L). Canc Biol Ther 9:122-33. |
Yang D, Wang MT, Tang Y, Chen Y, Jiang H, Jones TT, Rao K, Brewer GJ, Singh KK, Nie D (2010) Canc Biol Ther
Abstract: A common metabolic change in cancer is the acquisition of glycolytic phenotypes. Increased expression of glycolytic enzymes is considered as one contributing factor. The role of mitochondrial defects in acquisition of glycolytic phenotypes has been postulated but remains controversial. Here we show that functional defects in mitochondrial respiration could be induced by oncogenic H-RasQ61L transformation, even though the mitochondrial contents or mass was not reduced in the transformed cells. First, mitochondrial respiration, as measured by mitochondrial oxygen consumption, was suppressed in NIH-3T3 cells transformed with H-RasQ61L. Second, oligomycin or rotenone did not reduce the cellular ATP levels in the H-RasQ61L transformed cells, suggesting a diminished role of mitochondrial respiration in the cellular energy metabolism. Third, inhibition of glycolysis with iodoacetic acid reduced ATP levels at a much faster rate in H-RasQ61L transformed cells than in the vector control cells. The reduction of cellular ATP levels was reversed by exogenously added pyruvate in the vector control cells but not in H-RasQ61L transformed cells. Finally when compared to the HRasQ61L transformed cells, the vector control cells had increased resistance toward glucose deprivation. The increased resistance was dependent on mitochondrial oxidative phosphorylation since rotenone or oligomycin abolished the increased survival of the vector control cells under glucose deprivation. The results also suggest an inability of the H-RasQ61L transformed cells to reactivate mitochondrial respiration under glucose deprivation. Taken together, the data suggest that mitochondrial respiration can be impaired during transformation of NIH-3T3 cells by oncogeneic H-RasQ61L. • Keywords: Ras, Mitochondrial respiration, Glycolysis, Electron transport chain, Complex IV, Transformation, Cellular energy metabolism, ATP
• O2k-Network Lab: US IL Springfield Brewer GJ
Labels: MiParea: Respiration, mt-Biogenesis;mt-density
Pathology: Cancer
Organism: Mouse
Preparation: Intact cells Enzyme: Complex IV;cytochrome c oxidase Regulation: Aerobic glycolysis, ADP, Inhibitor, Substrate Coupling state: OXPHOS
HRR: Oxygraph-2k
