Research progress on the function of the amino acid transporter SLC1A3 and its regulation mechanism of action in the nervous system and mitochondria

Abstract

<p indent="0mm">The solute carrier family 1 member 3 (<italic>SLC1A3</italic>) gene encodes for excitatory amino acid transporter 1 (EAAT1), an important excitatory amino acid transporter. EAAT1 is mainly responsible for the transport of aspartate (Asp) and glutamate (Glu) in and out of the cell through the cell membrane, and plays an important role in regulating animal health and growth. To date, research on <italic>SLC1A3</italic> has mostly focused on its role in the nervous system and tumor tissues, whereas little is known about the regulation of <italic>SLC1A3</italic> in other systems and tissues. This paper reviews the expression, distribution, and biological function of <italic>SLC1A3</italic> in various animal tissues and organs. <italic>SLC1A3 </italic>exhibits the highest expression in the nervous system of animals. It participates in excitatory conduction in the synaptic cleft by transporting the neurotransmitter Glu, thus maintaining the normal functioning of the nervous system and preventing damage to the nervous system caused by the neurotoxic effects of Glu. <italic>SLC1A3</italic> is also widely distributed in the digestive, circulatory, motor, endocrine, and reproductive systems and plays an important role in regulating mitochondrial function, cell proliferation, metabolism, nutrition, and immunity. We analyzed the gene regulatory mechanism of <italic>SLC1A3</italic> in the nervous system and mitochondria. In the nervous system, <italic>SLC1A3</italic> is expressed by astrocytes and maintains a low concentration of extracellular Glu by transporting Glu from the synaptic cleft into the cell, thereby preventing glutamate-induced excitotoxicity in the nervous system. Reduced expression and function of <italic>SLC1A3</italic> induce neurodegeneration in the brain matter, thus creating a space for cancer cells to survive. Additionally, <italic>SLC1A3</italic> is responsible for the intracellular transport of Glu and Asp between the cytoplasm and mitochondria, as well as maintenance of the normal operation of the tricarboxylic acid (TCA) cycle and mitochondrial electron transport chain (ETC) to promote cell proliferation and restore cellular function. For example, <italic>SLC1A3</italic> helps cancer cells to survive under nutrient-limiting conditions by transporting Asp under conditions of cellular glutamine starvation. <italic>SLC1A3</italic> ensures high uptake of Glu in the heart to maintain the normal state of electron acceptors and the TCA cycle, thereby promoting the functioning of cardiomyocytes and protecting the heart under hypoxic or ischemic conditions. In case of ETC inhibition, an insufficient supply of electron acceptors in the cells inhibits <italic>de novo</italic> glutamine biosynthesis. <italic>SLC1A3</italic> replaces the electron acceptor in the ETC, thereby transporting Asp and restoring the anabolism of Asp, which is beneficial for cell proliferation. Finally, <italic>SLC1A3</italic> is expressed in different tissues and cells and exhibits a potential regulatory effect on the growth and metabolism of the body. <italic>SLC1A3</italic> can be used as a transporter of acidic amino acids, and in the urea cycle, TCA cycle, and the malate/aspartate shuttle to provide nutrition, relieve oxidative stress, and enhance immunity. Therefore, extensive research and discussion on the functioning of acidic amino acid transporters such as <italic>SLC1A3</italic> can provide a theoretical basis using them as key targets for regulating animal health and improving disease treatment.