Removal of ruptured lysosomes by autophagy is one of the mechanisms by which cells alleviate detrimental consequences of lysosome leakage and may prevent the initiation of signaling cascades that lead to cell death. In this issue of The EMBO Journal, Papadopoulos et al (2017) report an essential role of p97 and its cofactors in autophagic clearance of damaged lysosomes and provide evidences for the relevance of p97 in neurodegenerative conditions.
See also: C Papadopoulos et al (January 2017)
Lysosomes constitute the main compartment for terminal degradation of macromolecules from secretory, endocytic, autophagic, and phagocytic pathways. Their degradative properties are executed by various soluble acid hydrolases, whose combined actions maintain a constant removal of unwanted cellular material (Settembre et al, 2013). However, potent hydrolytic capacity of lysosomal enzymes can also cause a threat to the cellular integrity when released to the cytosol upon rupture of the lysosomal membrane, leading to cathepsin‐induced cell death. Lysosome membrane permeabilization (LMP) can occur due to endogenous stressors such as ROS, osmotic lysis, as a result of endosome to cytosol host cell invasion by bacteria and viruses, or as a consequence of direct membranolytic activity of incorporated chemical compounds and mineral crystals (Repnik et al, 2014). Autophagy is one of the potential mechanisms implicated in lysosome quality control and may prevent excessive cell death during LMP by sequestering membrane remnants (Hung et al, 2013; Maejima et al, 2013; Khaminets et al, 2016).
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