Evidences for the non-redundant function of A-type proteins ISCA1 and ISCA2 in iron-sulfur cluster biogenesis

Abstract : Iron-sulfur clusters (Fe-S) are essential cofactors involved in different cellular processes ranging from DNA metabolism to respiration. Assembly of Fe-S clusters and their insertion into acceptor proteins is performed by dedicated protein machineries. Despite the high conservation from bacteria to man, different functional and mechanistic aspects of the Fe-S biogenesis remain elusive. In the present work, the function of the two mammalian A-type proteins ISCA1 and ISCA2 that are implicated in Fe-S biogenesis was investigated in vivo. First, an extensive analysis coupling immunoprecipitations and mass spectrometry led to the identification of a direct binding between ISCA1 and ISCA2 as well as specific protein partners of each protein. Furthermore, knockdown experiments in the mouse using adeno-associated virus provided clear evidence of the non-redundant function of ISCA1 and ISCA2, since only ISCA1 was shown to be required for a specific subset of mitochondrial Fe-S proteins.
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Lena Kristina Beilschmidt. Evidences for the non-redundant function of A-type proteins ISCA1 and ISCA2 in iron-sulfur cluster biogenesis. Organisation et fonctions cellulaires [q-bio.SC]. Université de Strasbourg, 2014. Français. ⟨NNT : 2014STRAJ031⟩. ⟨tel-01297049⟩

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