Gamma rays induce a p53-independent mitochondrial biogenesis that is counter-regulated by HIF1α

• DOI: 10.1038/cddis.2013.187
• Publication Date: 2013-06-13T16:16:33Z
• Authors: A Bartoletti-Stella; E Mariani; I Kurelac; A Maresca; M F Caratozzolo; L Iommarini; V Carelli; L H Eusebi; A Guido; G Cenacchi; L Fuccio; M Rugolo; A Tullo; A M Porcelli; G Gasparre
• Keywords: Senescence; TFAM

Mitochondrial biogenesis is an orchestrated process that presides to the regulation of organelles homeostasis within a cell. We show γ-rays, at doses commonly used in radiation therapy for cancer treatment, induce increase mitochondrial mass and function, response genotoxic stress pushes cells into senescence, presence functional p53. Although main effector γ-rays p53-p21 axis, we demonstrated only indirectly regulated by p53, whose activation triggers murine double minute 2 (MDM2)-mediated hypoxia-inducible factor 1α (HIF1α) degradation, leading release peroxisome-proliferator activated receptor gamma co-activator 1β inhibition HIF1α, thus promoting biogenesis. Mimicking hypoxia HIF1α stabilization, fact, blunts as well induction p21-mediated cell indicating prevalence hypoxic over response. Finally, also vivo post-radiotherapy DNA copy number correlates with lack tissue, concluding this may be useful molecular tool infer trigger during radiotherapy, which lead failure senescence.