59] Inhibitors of lysosomal function

Abstract

A number of inhibitors are found to be useful in the study of lysosomal function. This chapter describes the inhibitors, which affect lysosomal function. The chapter also discusses weak-base (lysosomotropic) amines and the proteinase inhibitors, which are the most lysosome-specific of these, and the autophagy-inhibitory purines and some inhibitors that affect lysosomal function indirectly (microtubule poisons and protein synthesis inhibitors). Ammonia and the weakly basic alkylamines are lysosomotropic in the sense that, at low concentrations, they selectively accumulate in the lysosomes. The chapter also describes the biological effects of weak-base amines: interference with receptor-ligand dissociation and the recycling of receptors and membranes, inhibition of vacuolar membrane fusion and related processes, inhibition of lysosomal degradation, ionophores, proteinase-inhibitory peptides, vanadate, microtubule poisons, lectins and polymers, and protein synthesis inhibitors. Inhibitors of protein synthesis suppress the endogenous protein degradation in several cell types apparently by an action upon the lysosomal pathway. Despite their very general effects on the cell, the microtubule poisons may be useful as inhibitors of lysosomal function, acting differently from the other lysosome drugs.