Lysosomal Membrane Transport in Cellular Nutrition

A host of cellular nutrients are either synthesized within the cell itself or enter directly via transport across the plasma membrane. But a significant portion of the small molecules necessary for a cell's growth and metabolism require passage through the lysosome or a similar acidic vesicular compartment. These nutrients arrive in the lysosome by hydrolysis of macromolecules or by receptor-mediated endocytosis. They leave by carrier-mediated transport or, we speculate, by intermembrane transfer in the case of lipophilic substances. In either case, a vesicular membrane provides the key to communication between the lysosome and the cytosol, and that membrane now requires intensive study. The success of future pursuits in this area will be aided by an increased recognition of the importance of the lysosome-to-cytosol step in cellular metabolism. For example, investigators might ask how iron gets out of endosomes, or how thyroxine gets out of lysosomes. In addition, naturally occurring mutations, or inborn errors of metabolism, provide invaluable opportunities to delineate a normal pathway, using the mutant for comparison. Physician and scientists alike can advance our knowledge of lysosomal membrane transport by increasing their collective index of suspicion that unknown lysosomal storage disorders might represent transport defects, rather than strictly enzymatic defects.