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Oncogene-Induced Senescence: Role of Mitochondrial Dysfunction

  • Olga Moiseeva
  • Gerardo Ferbeyre
Chapter
Part of the Tumor Dormancy and Cellular Quiescence and Senescence book series (DOQU, volume 2)

Abstract

Mitochondrial biogenesis is activated in response to different signals and environmental stimuli. Recent data demonstrate an important role for mitochondrial biogenesis in the development of cellular senescence. Normal cellular response to increased energy demand after oncogene stimulation includes the induction of mitochondrial respiration. However, strong and prolonged activation of oxidative phosphorylation leads to oxidative stress, nuclear and mitochondrial DNA damage, mitochondrial dysfunction and senescence. Mutations in tumor suppressors in cooperation with activated oncogenes trigger the shift from mitochondrial respiration to aerobic glycolysis supplying the cells with ATP and metabolic substrates. It has been shown that the reverse shift has antiproliferative effect on cancer cells. As in normal proliferating cells mtDNA concentration is proportional to the oxidative capacity of the cell, the antitumor therapy can be based on the stimulation of mtDNA replication. It is expected that such therapy will stimulate mitochondrial respiration and additional disruption of oxidative phosphorylation will produce more free radicals, DNA damage response and senescence.

Keywords

Cancer cells Energy metabolism Mitochon-drial dysfunction Mitochondrial single-stranded DNA-binding protein (mtSSB) Oxidative phosphorylation (OXPHOS) Senescence-associated heterochromatin foci (SAHF) Senescence-associated secretory phenotype (SASP) Tumor development 

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Departmente de BiochimieUniversite de MontrealMontrealCanada

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