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Functional studies of Frataxin : relations with metal homeostasis and oxidatives stress

Abstract : The frataxin is a mitochondrial protein which is highly conserved during the evolution. The deficiency of frataxinin human induces a neurodegenerative disease: Friedreich’s ataxia. This protein was discovered in the nineties.However, its functions are always opened questions. It has been shown that frataxin participates in the assemblyof Fe-S cluster, as well as the iron homeostasis and cellular antioxidant system. The interactions between frataxinand others molecules, such as metals or proteins, are necessary for a better understanding of protein’s functions.In this work, we synthesized a yeast frataxin homologue (Yfh1) by DNA recombinant technique, and thenpurified it for cell free studies. Yeast flavohemoglobin (Yhb1), which is responsible for the detoxification of NO(an oxidative and nitrosative stress agent), was also isolated. We started by determining the thermodynamics andkinetics of the physiological interaction between Yfh1 and mitochondrial metals, such as Fe, Cu, Mn and Zn, aswell as the interaction with the gatekeepers in the anti-oxidative stress such as superoxide dismutases, CuZnSOD& MnSOD, and Yhb1. We underline here, in the first part the unspecific interaction of Yfh1 with mitochondrialmetals, and more especially the higher affinity of Yfh1 for copper and manganese than for iron. We also confirmthe remarkable participation of Yfh1 in the antioxidant system. Based on these observations, we assume thatfrataxin plays the role of a “regulator” in metal metabolism.
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Thi-Hong-Liên Han. Functional studies of Frataxin : relations with metal homeostasis and oxidatives stress. Other. Université Sorbonne Paris Cité, 2016. English. ⟨NNT : 2016USPCC288⟩. ⟨tel-01929004⟩

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