Facilitation of lysosome disruption by ATP at low pH

Abstract

HAYASHIet al.¹ reported that ATP stimulates in vitro the degradation of proteins at pH 4.5 by lysosomes which were intact at the start of the experiment. In accordance with our previous results, no effect was found at pH 5.0 (ref. 2). Although they found more rapid degradation by disrupted lysosomes, these authors concluded that the effect of ATP was not due to an increased labilisation of the lysosomal membrane, but that “ATP facilitates the pinocytotic engulfment of proteins into lysosomes and thereby stimulates proteolysis”. This conclusion was mainly based on experiments on non-sedimentable cathepsin D activity, discussed below. We have reinvestigated the effect of ATP on protein breakdown at different pH values, and found essentially the same results. Our evidence shows, however, that the increase of proteolysis is due to facilitation of lysosome disruption by ATP at pH 4.5.