Functional Amino Acids and Autophagy: Diverse Signal Transduction and Application

Abstract

Functional amino acids provide great potential for treating autophagy-related diseases by regulating autophagy. The purpose of the autophagy process is to remove unwanted cellular contents and to recycle nutrients, which is controlled by many factors. Disordered autophagy has been reported to be associated with various diseases, such as cancer, neurodegeneration, aging, and obesity. Autophagy cannot be directly controlled and dynamic amino acid levels are sufficient to regulate autophagy. To date, arginine, leucine, glutamine, and methionine are widely reported functional amino acids that regulate autophagy. As a signal relay station, mammalian target of rapamycin complex 1 (mTORC1) turns various amino acid signals into autophagy signaling pathways for functional amino acids. Deficiency or supplementation of functional amino acids can immediately regulate autophagy and is associated with autophagy-related disease. This review summarizes the mechanisms currently involved in autophagy and amino acid sensing, diverse signal transduction among functional amino acids and autophagy, and the therapeutic appeal of amino acids to autophagy-related diseases. We aim to provide a comprehensive overview of the mechanisms of amino acid regulation of autophagy and the role of functional amino acids in clinical autophagy-related diseases and to further convert these mechanisms into feasible therapeutic applications.

Study on the effects of rapamycin and the mTORC1/2 dual inhibitor OSI-027 on the metabolism of colon cancer cells based on UPLC-MS/MS metabolomics

“…Given the significant contribution of amino acid imbalance to metabolic reprogramming in tumor cells, we meticulously examined the metabolic changes of specific amino acids. Certain functional amino acids can modulate autophagy through the mTOR signaling pathway [28]. Acting as the building blocks for protein synthesis, amino acids fulfill diverse roles in energy production, nucleotide synthesis, and the maintenance of cellular redox homeostasis [29].…”

Dysregulation of acyl carnitines, pentose phosphate pathway and arginine and ornithine metabolism are associated with decline in intrinsic capacity in Chinese older adults

“…Two weeks of exercise with L-Arg supplement showed protective effects on the heart of aged mice, such as reducing myocardial cell damage, apoptosis and remodeling, improving antioxidant capacity, and reducing expression of pro-inflammatory markers like TNF-α, IL-1β, and IL-6 [ 44 ]. The inverse correlation of arginine and ornithine metabolism with IC (especially mobility and cognition) is possibly related to the chronic low-grade inflammation induced by Arg and related compounds [ 45 ], and the regulation of autophagy related to mammalian target of rapamycin complex 1 (mTORC1) [ 46 ].…”

Duality of Branched-Chain Amino Acids in Chronic Cardiovascular Disease: Potential Biomarkers versus Active Pathophysiological Promoters

“…A complex between Rag GTPases and mTORC1 is formed in the presence of amino acids translocating from the cytoplasm to the lysosomal membranes to further activate by Rheb [ 43 ]. The direct interaction with the Raptor part of mTORC1 is facilitated by leucyl-tRNA synthetase (LRS)’s interaction with Rag, resulting in the assembly of the RagA/B–RagC/D complex in their GTP/GDP-loading states (RagA/B-GTP and RagC/D-GDP) [ 39 , 44 ]. This explains why low levels or the absence of amino acids promote mTORC1 inactivation secondary to Rag transitions into an inactive state [ 45 ].…”