A proteomic analysis of lysosomal integral membrane proteins reveals the diverse composition of the organelle

Lysosomes are endocytic subcellular compartments that contribute to the degradation and recycling of cellular material. Using highly purified rat liver tritosomes (Triton WR1339-filled lysosomes) and an ion exchange chromatography/LC-tandem MS-based protein/peptide separation and identification procedure, we characterized the major integral membrane protein complement of this organelle. While many of the 215 proteins we identified have been previously associated with lysosomes and endosomes, others have been associated with the endoplasmic reticulum, Golgi, cytosol, plasma membrane, and lipid rafts. At least 20 proteins were identified as unknown cDNAs that have no orthologues of known function, and 35 proteins were identified that function in protein and vesicle trafficking. This latter group includes multiple Rab and SNARE proteins as well as ubiquitin. Defining the roles of these proteins in the lysosomal membrane will assist in elucidating novel lysosomal functions involved in cellular homeostasis and pathways that are affected in various disease processes.