Amino acid transporters revisited: New views in health and disease

Abstract

Amino acid transporters (AATs) are membrane-bound transport proteins that mediate transfer of amino acids into and out of cells or cellular organelles. AATs have diverse functional roles ranging from neurotransmission to acid-base balance, intracellular energy metabolism, and anabolic and catabolic reactions. In cancer cells and diabetes, dysregulation of AATs leads to metabolic reprogramming, which changes intracellular amino acid levels, contributing to the pathogenesis of cancer, obesity and diabetes. Indeed, the neutral amino acid transporters (NATs) SLC7A5/LAT1 and SLC1A5/ASCT2 are likely involved in several human malignancies. However, a clinical therapy that directly targets AATs has not yet been developed. The purpose of this review is to highlight the structural and functional diversity of AATs, their diverse physiological roles in different tissues and organs, their wide-ranging implications in human diseases and the emerging strategies and tools that will be necessary to target AATs therapeutically.

Keywords: Solute carriers (SLCs); acid-base balance; ammoniagenesis; autophagy; cancer; diabetes mellitus; energy metabolism; excitotoxicity; glutamine-glutamate cycle; inborn errors of metabolism; insulin and glucagon secretion; longevity; mTORC1/S6K1 pathway; membrane protein structure; membrane transport; metabolic acidosis; neurotransmission; pancreas.