Zeng_2025_Insect.Biochem.Mol.Biol_186_104447

Lysosomal Acid Lipase (LAL) is the key enzyme responsible for hydrolyzing cholesteryl esters and triglycerides within lysosomes. Its dysfunction is linked to various metabolic disorders in humans. However, its biological functions display tissue-specific heterogeneity, and the roles of its homologs in invertebrates remain largely unexplored. Herein, we demonstrated the lysosomal localization of acid lipase-1 (BmAL1) in Bombyx mori through fluorescent protein observation and Co-immunoprecipitation with the lysosomal membrane glycoprotein BmLAMP1. BmAL1 overexpression promoted lysosomal acidification, enhanced autophagy, and reduced lipid droplet (LD) formation after oleic acid or palmitic acid treatment. Conversely, BmAL1 knockout or knockdown inhibited lysosomal acidification, autophagic flux, and lipid degradation. Subsequently, immunoprecipitation coupled with LC-MS analysis revealed that the BmAL1-interacting proteins were mainly associated with metabolic and human-disease pathways. Notably, functional disruption of BmAL1-interacting protein BmHSP83/BmHSP90 (heat shock protein) compromised BmAL1-mediated lysosomal acidification, autophagy induction, lipid metabolism, and the physical interaction between BmAL1 and BmLAMP1. These data fill a critical gaps in LAL research in invertebrates, and highlight potential targets for the utilization of beneficial insects and the development of pest control strategies.