| Impairment of mitochondrial respiration in mouse fibroblasts by oncogenic H-RAS(Q61L). | |
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MedLine Citation:
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PMID: 19923925 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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(Q61L) 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(Q61L). Second, oligomycin or rotenone did not reduce the cellular ATP levels in the H-Ras(Q61L) 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(Q61L) 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-Ras(Q61L) transformed cells. Finally when compared to the HRas(Q61L) 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-Ras(Q61L) 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(Q61L). |
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Authors:
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Dianer Yang; Man-Tzu Wang; Yong Tang; Yakun Chen; Hongmei Jiang; Torrie T Jones; Krishna Rao; Gregory J Brewer; Keshav K Singh; Daotai Nie |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-01-21 |
Journal Detail:
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Title: Cancer biology & therapy Volume: 9 ISSN: 1555-8576 ISO Abbreviation: Cancer Biol. Ther. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-04-13 Completed Date: 2010-08-25 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 101137842 Medline TA: Cancer Biol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 122-33 Citation Subset: IM |
Affiliation:
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Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine and Simmons Cooper Cancer Institute, Springfield, IL, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Animals Antimycin A / pharmacology Cell Transformation, Neoplastic* Electron Transport / drug effects Energy Metabolism / drug effects Fibroblasts / metabolism* Genes, ras* Glucose / metabolism Glycolysis / drug effects Iodoacetic Acid / pharmacology Mice Mitochondria / drug effects, metabolism* Mutation, Missense NIH 3T3 Cells / metabolism Oligomycins / pharmacology Oncogene Protein p21(ras) / genetics, physiology* Oxidative Phosphorylation / drug effects Oxygen Consumption / drug effects Point Mutation Pyruvic Acid / pharmacology Rotenone / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA121904-10/CA/NCI NIH HHS; R01 CA121904-11/CA/NCI NIH HHS; R01AG013435/AG/NIA NIH HHS; R01CA121904/CA/NCI NIH HHS; R01CA131445/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Oligomycins; 127-17-3/Pyruvic Acid; 50-99-7/Glucose; 56-65-5/Adenosine Triphosphate; 64-69-7/Iodoacetic Acid; 642-15-9/Antimycin A; 83-79-4/Rotenone; EC 3.6.5.2/Oncogene Protein p21(ras) |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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