La fonction mitochondriale dans un modèle murin de Porphyrie Aiguë Intermittente (PAI)

Abstract : Hereditary porphyrias are a group of metabolic disorders of the haem biosynthesis pathway, the most severe and important porphyria is the Acute Intermittent Porphyria (AIP). Several metabolic links exist between haem biosynthesis and mitochondria, which is an organelle specialized in energy production. The aim of this work was to examine the impact of the acute attack of AIP on the mitochondrial energetic function. We have shown in a mice model of AIP, with deficiency in the hydroxymethylbilane synthase (HMBS), a mitochondrial metabolic dyfunction, an important alteration in the mitochondrial respiratory complexes activity, and those of Krebs cycle. This deficiency concerned the mice at basal state and after induction by phenobarbital in different tissus (liver, skeletal muscle and brain). In vitro, the administration of delta-aminolevulinic acid, a precursor of haem accumulating in AIP caused a dose-dependent impairment of mitochondrial function with an overproduction of reactive oxygen species (ROS). Our results suggest that acute attack of AIP alters the mitochondrial function in vivo and in vitro. This new data allows to better understand the pathophysiology and the clinical expression of this disease.
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Chadi Homedan. La fonction mitochondriale dans un modèle murin de Porphyrie Aiguë Intermittente (PAI). Médecine humaine et pathologie. Université d'Angers, 2015. Français. ⟨NNT : 2015ANGE0077⟩. ⟨tel-02280794⟩

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