| First Author | Douarre C | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 7 | Pages | e41094 |
| PubMed ID | 22911747 | Mgi Jnum | J:189886 |
| Mgi Id | MGI:5447214 | Doi | 10.1371/journal.pone.0041094 |
| Citation | Douarre C, et al. (2012) Mitochondrial topoisomerase I is critical for mitochondrial integrity and cellular energy metabolism. PLoS One 7(7):e41094 |
| abstractText | BACKGROUND: Mitochondria contain their own DNA genome (mtDNA), as well as specific DNA replication and protein synthesis machineries. Relaxation of the circular, double-stranded mtDNA relies on the presence of topoisomerase activity. Three different topoisomerases have been identified in mitochondria: Top1mt, Top3alpha and a truncated form of Top2beta. METHODOLOGY/PRINCIPAL FINDINGS: The present study shows the importance of Top1mt in mitochondrial homeostasis. Here we show that Top1mt-/- murine embryonic fibroblasts (MEF) exhibit dysfunctional mitochondrial respiration, which leads decreased ATP production and compensation by increased glycolysis and fatty acid oxidation. ROS production in Top1mt-/- MEF cells is involved in nuclear DNA damage and induction of autophagy. Lack of Top1mt also triggers oxidative stress and DNA damage associated with lipid peroxidation and mitophagy in Top1mt-/- mice. CONCLUSION/SIGNIFICANCE: Together, our data implicate Top1mt for mitochondrial integrity and energy metabolism. The compensation mechanism described here contributes to the survival of Top1mt-/- cells and mice despite alterations of mitochondrial functions and metabolism. Therefore, this study supports a novel model for cellular adaptation to mitochondrial damage. |
