COMMUNICATION CELLULAR ADAPTATION TO AMINO ACID AVAILABILITY: MECHANISMS INVOLVED IN THE REGULATION OF GENE EXPRESSION

In mammals, the impact of nutrients on gene expression has become an important area of research. Nevertheless, the current understanding of amino acid-dependent control of gene expression is limited. Amino acids have multiple and important functions, so their homeostasis has to be finely maintained. However, the amino acidemia can be affected by certain nutritional conditions or various forms of aggres-sion. It follows that mammals have to adjust several of their physiological functions involved in the adap-tation to amino acid availability by regulating expression of numerous genes. The aim of this review is to examine the role of amino acids in regulating mammalian gene expression and physiological functions. A limitation for several amino acids strongly increases the expression of target genes such as IGFBP-1, CHOP and asparagine synthetase (AS) genes. The molecular mechanisms involved in the regulation of CHOP and AS gene transcription in response to amino acid starvation have been partly identified. Particularly, a signalling pathway requiring the protein kinase GCN2 and the transcription factor ATF4 has been described to sense the amino acid limitation. In case of an amino acid imbalanced food source, this pathway has been shown to decrease food intake by activating a neuronal circuit. Taken together, the results discussed in this review demonstrate that amino acids by themselves can act as “signal