AI Article Synopsis
- Lysosomal membrane damage can lead to serious conditions like degenerative diseases, infections, and cancer, where cells may either repair lysosomes or initiate their degradation.
- If repair is unsuccessful, lysosomes are tagged with ubiquitin, triggering a selective form of autophagy called lysophagy to clear damaged lysosomes.
- The review focuses on how cells detect damage, the roles of ubiquitination and autophagy in this process, and the additional regulatory mechanisms involving proteins like VCP/p97, highlighting the decision-making between lysosome repair and degradation.
Article Abstract
Lysosomal membrane permeabilization or full rupture of lysosomes is a common and severe stress condition that is relevant for degenerative disease, infection and cancer. If damage is limited, cells can repair lysosomes by means of the endosomal sorting complex required for transport (ESCRT) machinery. Presumably, if repair fails, lysosomes are tagged with ubiquitin to initiate clearance by selective macroautophagy, termed lysophagy. Accumulating evidence suggests damage-induced exposure of luminal glycans to the cytosol as the key trigger for ubiquitination. In this review, we discuss recent data on cellular damage sensing, the underlying ubiquitination and autophagy machinery as well as additional layers of regulation such as processing of ubiquitinated proteins by the AAA-ATPase VCP/p97. We conclude with thoughts on how these mechanisms may regulate decision making between lysosome repair and lysophagy.
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| http://dx.doi.org/10.1016/j.jmb.2019.08.010 | DOI Listing |
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