Mechanism Of Lysophosphatidylcholine And Phospholipase A₂ Induced Lysosome Destabilization

Lysosomal disintegration can cause losses of its physiological functions and cytotoxic effects on living cells. As reported previously, some environmental factors can affect lysosomal stability. However, the physiological factors and mechanisms of the event remain to be elucidated. A series of studies testified that cytosolic lysoPC and PLA2 were enhanced in certain cellular pathological changes. Whether they can influence lysosomal membrane lipids and destabilize lysosomes is still unclear.In this study, we established that lysoPC and PLA2 can injure lysosomes and elucidated the related mechanisms of lysosomal destabilization. By measuring the free activity of lysosomalβ-hexosaminidase, their membrane potential, proton leakage, intra-lysosomal pH and their enzyme latency loss in hypotonic sucrose medium. We demonstrated that lysoPC and PLA2 could increase the lysosomal permeability to both potassium ions and protons, and enhance the lysosomal osmotic sensitivity. These changes in the lysosomal membrane properties promoted influx of potassium ions into the lysosomes via K+/H+ exchange. The resulted osmotic imbalance across the membranes osmotically destabilizes the lysosomes and led to losses of the lysosomal integrity.