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Étude des évènements mitochondriaux impliqués dans le contrôle de l'apoptose par rbf1, l'homologue de drosophile du gène suppresseur de tumeur rb

Abstract : The gene rb is the first tumor suppressor discovered in humans. Its prevents the appearance of tumors by regulating negatively the cell cycle. The role of pRb in apoptosis is more complex and the molecular mechanisms triggered by this transcription factor are not completely elucidated. There is a rb homologue in drosophila: rbf1. I participated in the characterization of mitochondrial events induced during activation of apoptosis by Rbf1 in a proliferating tissue of this model organism, the wing disc. In this apoptosis pathway, the Debcl protein, the only drosophila pro-apoptotic member of the Bcl-2 family, is activated and induces recruitment and oligomerization of Drp1, the main effector of mitochondrial fission. This triggers the mitochondrial fragmentation and the accumulation of mitochondrial reactive oxygen species (ROS). Both events participate to the transmission of the apoptotic signal. I have also been able to highlight the implication of factors involved in maintaining mitochondrial quality control which ensures the integrity of the mitochondria and, if necessary, triggers the degradation of damaged elements by mitophagy. Finally, I have contributed to the study of the links between translation and apoptosis induced by Rbf1. In this study, we show that the Poly-A Binding Protein (PABP) can suppress the Rbf1-induced notch phenotype in adults while cell death induced during larval stage was not inhibited but increased. These results prompted us to study the compensation mechanisms induced by the translational apparatus, which allowed us to show that a mRNA translation-related mechanism could counteract the loss of tissue resulting from Rbf1-induced apoptosis independently of apoptosis inhibition.
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Submitted on : Monday, October 29, 2018 - 5:02:08 PM
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Vincent Ruby. Étude des évènements mitochondriaux impliqués dans le contrôle de l'apoptose par rbf1, l'homologue de drosophile du gène suppresseur de tumeur rb. Génétique animale. Université Paris-Saclay, 2018. Français. ⟨NNT : 2018SACLV039⟩. ⟨tel-01908006⟩

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