Metabolic Regulation by Leucine of Translation Initiation Through the mTOR-Signaling Pathway

Recent findings have demonstrated that the branched-chain amino acid leucine can activate the translational regulators, phosphorylated heat- and acid-stable pro-tein regulated by insulin (PHAS-I) and p70 S6 kinase (p70s6k), in an insulin-independent and rapamycin-sen-sitive manner through mammalian target of rapamycin (mTOR), although the mechanism for this activation is undefined. It has been previously established that leucine-induced insulin secretion by -cells involves increased mitochondrial metabolism by oxidative decar-boxylation and allosteric activation of glutamate dehy-drogenase (GDH). We now show that these same intramitochondrial events that generate signals for leucine-induced insulin exocytosis are required to acti-vate the mTOR mitogenic signaling pathway by -cells