Abstract
We previously found that mouse mitochondrial DNA (mtDNA) with a G13997A mutation (G13997A mtDNA) controls not only the transformation of cultured lung carcinoma cells from poorly metastatic into highly metastatic cells, but also the transformation of lymphocytes into lymphomas in living C57BL/6 (B6) mice. Because the nuclear genetic background of the B6 strain makes the strain prone to develop lymphomas, here we examined whether G13997A mtDNA independently induces lymphoma development even in mice with the nuclear genetic background of the A/J strain, which is not prone to develop lymphomas. Our results showed that the B6 nuclear genetic background is required for frequent lymphoma development in mice with G13997A mtDNA. Moreover, G13997A mtDNA in mice did not enhance the malignant transformation of lung adenomas into adenocarcinomas or that of hepatocellular carcinomas from poorly metastatic into highly metastatic carcinomas. Therefore, G13997A mtDNA enhances the frequency of lymphoma development under the abnormalities in the B6 nuclear genome, and does not independently control tumor development and tumor progression.
Highlights
Mitochondrial respiration defects and the resultant enhanced glycolysis under normoxia, that is, the Warburg effect, enable cell growth under hypoxia, and are thought to be involved in tumor development [1,2,3,4]
No tumor development was observed in transmitochondrial mito-mice-COI6589 (B6mtCOI6589) with T6589C mitochondrial DNA (mtDNA) [14]. Because these mice expressed respiration defects and the Warburg effect [15], but did not overproduce reactive oxygen species (ROS), we proposed that ROS overproduction but not the Warburg effect would be responsible for high frequency lymphoma development [14]
The results suggest that G13997A mtDNA enhances the frequency of lymphoma development that is primarily caused by abnormalities in the B6 nuclear genome
Summary
Mitochondrial respiration defects and the resultant enhanced glycolysis under normoxia, that is, the Warburg effect, enable cell growth under hypoxia, and are thought to be involved in tumor development [1,2,3,4]. Because pathogenic mtDNA mutations induce mitochondrial respiration defects and the Warburg effect, age-associated accumulation of pathogenic. G13997A mtDNA Induces Lymphoma in Mice with B6 Nuclear Background study design, data collection and analysis, decision to publish, or preparation of the manuscript
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