PP05 focuses on understanding the physiological function of lysosomal lipid hydrolysis in various cells and tissues. Pronounced accumulation of cholesteryl esters but only low accumulation of triacylglycerols (TG) in macrophages and livers of Lal-deficientmice suggested the existence of additional enzyme(s) that hydrolyze lysosomal TGs. PP05 aims to characterize the TG-degrading enzymes in the lysosome identified in funding period 1. In addition, PP05 will elucidate which cells can take up functional lysosomal lipid hydrolases, quantitate the percentage of fatty acids from different pathways that are utilized by β-oxidation for energy production, and determine whether macrophages are responsible for lysosomal lipid accumulation in the small intestine of Lal-deficient mice.
