Permeability properties of lysosomal membranes.

Lysosomes are involved in the cellular degradation of material either initially present in the cell or brought into the cell by phagocytosis or endocytosis. This degradative process, which occurs in an acidic environment, produces metabolites such as peptides and amino acids~ nucleos ides , and sugars which may subsequently accumulate within the lysosome. It is therefore important for osmotic reasons, and for optimal uti l ization of these metabolites, to have a system whereby the degradative products can pass through the lysosomal membrane. This can be achieved either by passive diffusion or via a specific transport mechanism. Furthermore, maintenance of the acidic mi l ieu necessa ry for op t imal a c t i v i t y of the ]ysosomal enzymes requires concentration of hydrogen ions within the lysosome. This hydrogen-ion gradient may be maintained either by a Gibbs-Donnan equilibrium or via an ATP-dependent proton pump in the lysosomal membrane. It is these permeability and hydrogen-ion-concentrating properties of the lysosomal membrane which will be discussed in this review. Our interest in the mechanism by which the products of lysosomal digestion cross the lysosomal membrane to reach the cytosol arose from a hypothesis concerning the evolutionary origins of polypeptide hormones . Most polypeptide hormones are synthesized as propolypeptides which are cleaved at sites usually marked by pairs of basic amino acids (Docherty & Steiner, 1992). In considering the problem posed by the existence of prohormones~ it was suggested that they could be explained if the evolutionary origin of polypeptide hormones was from a more p r imi t ive process of lysosomal proteolysis in u n i c e l l u l a r organisms (Hales~ 1978~ Hales & Docher ty , 1979). Polypeptide fragments produced by this means within the lumen of the secondary lysosome would potentially be capable of interaction with m e m b r a n e components in the structure of the secondary lysosomal membrane. Such membrane proteins could include plasma-membrane t r a n s p o r t e r s . One of the most important processes regulated by p o l y p e p t i d e hormones is membrane t ranspor t . It was therefore suggested that the membrane of the secondary lysosome would contain transport mechanisms. Studies on the permeability properties of the lysosomal membrane to metabolites such as sugars and amino acids had up to that t ime been interpreted as indicative of simple diffusion (Reijngoud & Tager, 1977). We therefore undertook a reinvestigation of the problem as it related to sugar permeability. In this review we describe the methods available for the study of metabolite permeability of lysosomes and