Mitochondrial transcription factor A regulated ionizing radiation-induced mitochondrial biogenesis in human lung adenocarcinoma A549 cells

• Published in: Journal of radiation research Vol. 54; no. 6; pp. 998 - 1004
• Main Authors: Yu, Jing, Wang, Qisen, Chen, Ni, Sun, Yuxiang, Wang, Xiaofei, Wu, Lijun, Chen, Shaopeng, Yuan, Hang, Xu, An, Wang, Jun
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-11-2013
• Subjects: Adenocarcinoma; Adenocarcinoma - pathology; Adenocarcinoma - physiopathology; Biology; Biosynthesis; Cell Line, Tumor; Cells (Biology); Cytochrome c; Cytochrome oxidase; Deoxyribonucleic acid; DNA Copy Number Variations - genetics; DNA, Mitochondrial - genetics; DNA-Binding Proteins - metabolism; Dose-Response Relationship, Radiation; Electron Transport Complex IV - metabolism; Human; Humans; Ionizing radiation; Lungs; Maintenance; Mitochondria; Mitochondrial DNA; Mitochondrial Proteins - metabolism; Mitochondrial Turnover - radiation effects; Oxidase; Radiation Dosage; RNA; Transcription Factors - metabolism; Up-Regulation - radiation effects; Vertebrates; mitochondrial transcription factor A; mitochondrial biogenesis; mitochondrial DNA; ionizing radiation
• ISSN: 0449-3060; 1349-9157
• DOI: 10.1093/jrr/rrt046

Mitochondrial transcription factor A (TFAM), the first well-characterized transcription factor from vertebrate mitochondria, is closely related to mitochondrial DNA (mtDNA) maintenance and repair. Recent evidence has shown that the ratio of mtDNA to nuclearDNA (nDNA) is increased in both human cells and murine tissues after ionizing radiation (IR). However, the underlying mechanism has not as yet been clearly identified. In the present study, we demonstrated that in human lung adenocarcinoma A549 cells, expression of TFAM was upregulated, together with the increase of the relative mtDNA copy number and cytochrome c oxidase (COX) activity after -particle irradiation. Furthermore, short hairpin RNA (shRNA)-mediated TFAM knockdown inhibited the enhancement of the relative mtDNA copy number and COX activity caused by -particles. Taken together, our data suggested that TFAM plays a crucial role in regulating mtDNA amplification and mitochondrial biogenesis under IR conditions.