Cellular and animal indispensable amino acid limitation responses and health promotion. Can the two be linked? A critical review

Abstract

Cellular growth repression can mediate positive health outcomes by improving resistance while delaying the manifestation and decelerating the progression, of chronic diseases. Sensing systems that respond to amino acid limitation are, the general control non-derepressible kinase 2 (GCN2), the mammalian target of rapamycin (mTOR; namely mammalian target of rapamycin complex 1), the extracellular signal-regulated kinase (ERK)–mitogen-activated protein kinase pathway, the adenosine 5-mono-phosphate-activated protein kinase system. GCN2 particularly, under limiting essential amino acid conditions, activates the integrated stress response (ISR) causing selective up- /down-regulation of pro-survival/pro-apoptotic genes, respectively, rendering beneficial adaptation responses to amino acid limitation. This review attempts to bridge the link between molecular events and mechanisms observed at the cellular level with the potential health benefits possibly achieved at the whole organism level. The article describes mechanisms of essential amino acid sensing and provides a discussion on relevant research that suggests a potential role of essential amino acid sensing for promoting health.

Keywords::

• indispensable amino acids
• integrated stress response
• eIF2α
• GCN2
• mTOR
• 4E-BP1
• AMPK

Declaration of interest : The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.