Thesis presented November 22, 2011

Abstract:
ATAD3A is part of a novel family of mitochondrial AAA+ ATPase (ATPases Associated to diverse cellular Activities) specific to the multicellular eukaryotes (Gilquin et al. Mol Cell Biol, 2010a). In the laboratory, we have identified ATAD3A as a specific target for the Ca²⁺/Zn²⁺-binding S100B protein (Gilquin et al. Mol Cell Biol, 2010b). In the ​Hominidae, there is a second member of the ATAD3 family, the mitochondrial protein ATAD3B. The aim of my thesis was to solve the mitochondrial topology of ATAD3A and ATAD3B and to study their functions and interactions. We have shown that these two proteins are anchored in the inner mitochondrial membrane at the contact sites with the external membrane and that they form hexameric complexes. We have then shown that ATAD3B is specifically expressed in the human embryonic stem cells and is re-expressed in iPs (induced Pluripotent stem cell) and certain cancer cell lines. Complimentary studies were done using the down regulation of ATAD3B by shRNA and expression of dominant-negative ATAD3A mutants in the human lung cancer cell line, H1299. Our results suggest that ATAD3B interacts and forms hetero-oligomers with ATAD3A. ATAD3B seems to behave like a dominant negative of ATAD3A. To have a better understanding of the function of ATAD3A in vivo, we developed models in Drosophila with which results show that ATAD3A is required for cell growth and organism development.

Keywords:
Mitochondria, Drosophila, Stem cell, ATAD3A, ATAD3B

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