Lysosomal protein SLC38A9 regulates arginine-mediated autophagy, ER stress, and apoptosis in abalone Haliotis discus hannai

The diverse functions of arginine make it an indispensable component for overall cellular health and function. This study evaluated the effect and mechanism of arginine on autophagy, endoplasmic reticulum (ER) stress, and apoptosis, which are key pathways that regulate cell homeostasis and fate. The results showed that the imbalance of arginine (deficiency or excess) inhibited the growth of cells and disrupted cell homeostasis by increasing the level of autophagy, ER stress, as well as apoptosis. This in turn affects cell growth, homeostasis, and fate. Furthermore, the present study validated the lysosomal protein localization and arginine binding ability of the solute carrier family 38 member 9 (SLC38A9). This study also demonstrated SLC38A9 interaction with Ras-related GTP binding (Rag) complexes, the core sensor of amino acid signaling in the mechanistic target of rapamycin (mTOR) signaling pathway. This provides evidence for the sensing of arginine signals by SLC38A9. Furthermore, the siRNA-mediated knockdown of slc38a9 exacerbated the extent of the autophagy, ER stress, and apoptosis, while stable expression of SLC38A9 was found to alleviate these processes, as well as the disruption of cell homeostasis and function caused by arginine deficiency. The present study comprehensively explored the function of arginine in cell growth and fate, revealed the vital role and mechanism of SLC38A9 in arginine sensing, and expanded the understanding of the multiple functions of SLC38A9 in abalone.