Consequences of ATAD3 Hemizygosity in C57Bl6j Mice

International audience ; ATAD3 is a mitochondrial ATPase involved in reticulum/mitochondria interactions and cholesterol transport and essential for mitochondrial biogenesis as vital at an early stage of development but still with unknown molecular functions.To evaluate the role of ATAD3 expression at the animal scale we used ATAD3 hemizygote mice of C57bl6j genetic background to test the impact on mitochondrial biogenesis. For this goal, we studied two physiological capacities involving mitochondrial biogenesis: (i) training efficiency for running performance, with males, and (ii) reaction to high-fat/high-sucrose diets with females.We found that ATAD3 hemizygosity decreases male’s heart and body weights, especially at the adipose tissue level, and almost suppress running training improvement, but surprisingly increases the gripping strength and modifies the circadian activity. These phenotypes are associated with a lower mitochondrial mass and a major increase of Acetyl-CoA Carboxylase (ACC) phosphorylation ratio status in muscles. ATAD3 hemizygosity favors body weight increase under high-fat/high-sucrose diet in females, especially at the adipose tissue level, and induces a major increase of ACC phosphorylation status in the adipose tissue.We show therefore that ATAD3 gene does not present allelic compensation, or haplo-sufficiency, under training and high-calorie dieting phases in mice and that ATAD3 hemizygosity is potentially involved in pathologies such as obesity and not severe myopathies.