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Mechanism of Lysophosphatidylcholine-Induced Lysosome Destabilization

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Abstract

Lysosomal destabilization is critical for the organelle and living cells. Phospholipase A2 (PLA2) was shown to be able to destabilize lysosomes under some conditions. By what mechanism the enzyme affects lysosomal stability is not fully studied. In this study, we investigated the effects of lysophosphatidylcholine (lysoPC), a PLA2-produced lipid metabolite, on lysosomal ion permeability, osmotic sensitivity and stability. By measuring lysosomal β-hexosaminidase free activity, membrane potential, proton leakage and their enzyme latency loss in hypotonic sucrose medium, we established that lysoPC could increase the lysosomal permeability to both potassium ions and protons and enhance lysosomal osmotic sensitivity. These changes in lysosomal membrane properties promoted entry of potassium ions into lysosomes via K+/H+ exchange. The resultant osmotic imbalance across the membranes led to losses of lysosomal integrity. The enhancement of lysosomal osmotic sensitivity caused the lysosomes to become more liable to destabilization in osmotic shock. These results suggest that lysoPC may play a key role in PLA2-induced lysosomal destabilization.

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Acknowledgement

supported by project 30470446 from the National Natural Science Foundation of China.

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Authors and Affiliations

  1. Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China

    Lin Sun & Guo-Jiang Zhang

  2. School of Science, Hebei University of Technology, Tianjin, 300130, People’s Republic of China

    Jin-Shan Hu

  3. Capital Normal University, Beijing, 100037, People’s Republic of China

    Ying-Bin Li

  4. Institute of Cell Biology, Beijing Normal University, Beijing, 100875, People’s Republic of China

    Jiong-Wei Wang

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  1. Jin-Shan Hu
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Correspondence to Guo-Jiang Zhang.

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Hu, JS., Li, YB., Wang, JW. et al. Mechanism of Lysophosphatidylcholine-Induced Lysosome Destabilization. J Membrane Biol 215, 27–35 (2007). https://doi.org/10.1007/s00232-007-9002-7

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