Lysosomal destabilization is a critical event not only for the organelle but also for living cells. However, what factors can affect lysosomal stability is not fully studied. In this work, we investigated the effects of phosphatidic acid on the lysosomal integrity. Through the measurements of lysosomal β -hexosaminidase free activity, intralysosomal pH, leakage of lysosomal protons and lysosomal latency loss in hypotonic sucrose medium, we established that phosphatidic acid could increase the lysosomal permeability to K~+and H.+, and enhance the lysosomal osmotic sensitivity. Treatment of lysosomes with PA promoted entry of K~+ into the organelle via K~+/H~+ exchange, which could produce osmotic stresses and osmotically destabilize the lysosomes. In addition, PA-induced increase in the lysosomal osmotic sensitivity caused the lysosomes to become more liable to destabilization in osmotic shocks. In conclusion, the results suggest that phosphatidic acid may play a role in the lysosomal destabilization. |