Harald Stenmark Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
Because of their acidity and high content of calcium and hydrolytic enzymes, damaged lysosomes represent a hazard to the cell. Such damage can be caused by a number of conditions, including detergents, cationic amphiphilic drugs, lysosomotropic agents, and phagocytosed microorganisms and mineral crystals. To limit toxicity, the cell is equipped with mechanisms to counter the damage caused by leaky lysosomes. A well-described mechanism is lysophagy, by which damaged lysosomes are sequestered by autophagosomes (Maejima et al., 2013). We are currently investigating the possibility that a repair mechanism for damaged lysosomes exists, and that lysophagy only becomes activated in cases where lysosomes are too damaged that the repair pathway works.
Reference: Maejima, I., Takahashi, A., Omori, H., Kimura, T., Takabatake, Y., Saitoh, T., Yamamoto, A., Hamasaki, M., Noda, T., Isaka, Y., et al. (2013). Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury. EMBO J 32, 2336-2347.
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