Amino Acids in Endoplasmic Reticulum Stress and Redox Signaling

Proteins are the chains of amino acids linked via peptide bonds. In cells, newly synthesized proteins are modified and folded in the endoplasmic reticulum (ER) and matured to be functional proteins before they are transported to other tissues or organs. In addition to protein synthesis, the ER is also a stress-sensing organelle for diverse biological functions, such as calcium storage, lipid synthesis, and cellular metabolism. Nutrient deprivation, accumulation of reactive oxygen species, and other intracellular insults can activate ER stress and unfolded protein response (UPR) to restore homeostasis. Dysfunction of the ER influences cellular physiology and metabolism, and contributes to the pathogenesis of various diseases. Amino acids are the building blocks for proteins of eukaryotic organisms. Both in vivo and in vitro studies have found that amino acids can function as signaling molecules to regulate gene expression, cell proliferation and apoptosis, immune response, and antioxidant capacity in numerous biological processes. Importantly, several lines of studies have indicated that amino acids regulate the abundances of proteins implicated in UPR and the redox state, therefore restoring the intracellular homeostasis. Amino acids play an important role in regulating ER stress and redox homeostasis in animal cells for their survival, growth, and development.