Abstract
REDD1 is a ubiquitous and conserved protein, which is expressed in response to numerous stresses and pathologies responsible of muscle atrophy, a parameter correlated with patient mortality. REDD1 is known to inhibit Akt/mTORC1 pathway which controls synthesis of proteins (the major component of muscle) and other macromolecules such as ribosome, nucleotide or glycogen. Our work shows on a mice model that REDD1 inhibits protein synthesis, leading to skeletal muscle atrophy, and reduces muscle glycogen storage. However, REDD1 deletion is responsible of an increase in basal metabolism, a reduction of exercise capacity and an exacerbation of hypoxia-induced skeletal muscle atrophy. These metabolic alterations are not associated with a mitochondrial dysfunction but rather with an hyper activation of the Akt/mTORC1 pathway which is responsible for the stimulation of energy demanding processes. Altogether, these results strongly suggest that REDD1 acts for moderating ATP demand in energetic stress conditions.