Jose 2012 Thesis Université Victor Segalen Bordeaux - France
|Jose C (2012) Rôle des mitochondries dans la tumorigénèse: implications pour le traitement du cancer. Thesis Université Victor Segalen Bordeaux - France 272pp.|
Abstract: In the 1920s, Otto Warburg first hypothesized that mitochondrial impairment is a leading cause of cancer although he recognized the existence of oxidative tumors. Likewise, Weinhouse (1950) and others found that deficient mitochondrial respiration is not an obligatory feature of cancer and Peter Vaupel suggested in the 90s that tumor oxygenation rather than OXPHOS capacity was the limiting factor of mitochondrial energy production in cancer. This thesis and recent studies now clearly indicate that mitochondria are highly functional in tumors and the field of oncobioenergetic identified Myc, Src, Oct1 and RAS as pro-OXPHOS oncogenes. In addition, cancer cells adaptation to aglycemia, metabolic symbiosis between hypoxic and non-hypoxic tumor regions as well the reverse Warburg hypothesis support the crucial role of mitochondria in the survival of a subclass of tumors. Therefore, mitochondria are now considered as potential targets for anti-cancer therapy and tentative strategies including a bioenergetic profile characterization of the tumor and the subsequent adapted bioenergetic modulation could be considered for cancer killing. We show anti-cancer effects of two mitochondrial modulators and dissect their mechanism of action.
• Keywords: Mitochondria, Cancer, Metabolic remodeling, Bioenergetics, Oxidative phosphorylation, Therapeutic approaches
• O2k-Network Lab: FR Bordeaux Rossignol R
Labels: MiParea: Respiration, mt-Medicine, mt-Awareness Pathology: Cancer
Organism: Human Tissue;cell: Other cell lines, HeLa Preparation: Intact cells, Permeabilized cells
Coupling state: LEAK, ROUTINE, OXPHOS, ET Pathway: N, S HRR: Oxygraph-2k