The direct cause of photodamage-induced lysosomal destabilization

Whether membrane lipid photoperoxidation is the immediate cause for lysosomal lysis is still unclear. In this study, we investigated the direct causal factor of photoinduced lysosomal destabilization in a K+-containing solution. Methylene blue (MB)-mediated photodamage caused lysosomal membrane lipid peroxidation and loss of membrane fluidity. Compared with unirradiated lysosomes, the photodamaged lysosomes significantly lost enzyme latency in an isotonic K+-containing solution during a 20-min period of incubation. It indicates an increase in lysosomal K+ permeability. The inward K+ permeation of photodamaged lysosomes was further proved by a K+-induced elevation of internal membrane potential. In addition, the photodamaged lysosomes displayed an increased osmotic sensitivity, showing that MB-mediated photodamage promotes lysosomal osmotic fragility. Although these photoinduced alterations occurred, the lysosomes were relatively stable in an isotonic sucrose medium. In contrast, the organelle destabilized in a photodamage-dependent fashion in an isotonic K+-containing solution. The results indicate that membrane lipid peroxidation does not definitely destabilize lysosomes. The direct cause for the lysosomal destabilization is photoinduced osmotic imbalance across its membrane via an increased K+ uptake, while the increase in osmotic sensitivity favors the destabilization of photodamaged lysosomes.