Amino acid deprivation induces translation of branched-chain alpha-ketoacid dehydrogenase kinase.

Leucine, isoleucine, and valine are used by cells for protein synthesis or are catabolized into sources for glucose and lipid production. These branched-chain amino acids influence proteolysis, hormone release, and cell cycle progression along with their other metabolic roles. The branched-chain amino acids play a central role in regulating cellular protein turnover by reducing autophagy. These essential amino acids are committed to their catabolic fate by the activity of the branched-chain alpha-ketoacid dehydrogenase complex. Activity of the branched-chain alpha-ketoacid dehydrogenase complex is regulated by phosphorylation/inactivation of the alpha-subunit performed by a complex specific kinase. Here we show that elimination of the branched-chain amino acids from the medium of cultured cells results in a two- to threefold increased production of the branched-chain alpha-ketoacid dehydrogenase kinase with a decrease in the activity state of the branched-chain alpha-ketoacid dehydrogenase complex. The mechanism cells use to increase kinase production under these conditions involves recruitment of the kinase mRNA into polyribosomes. Promoter activity and the steady-state concentration of the mRNA are unchanged by these conditions.