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Review
. 2025 Sep;35(9):761-772.
doi: 10.1016/j.tcb.2025.02.007. Epub 2025 Mar 11.

Cellular homeostatic responses to lysosomal damage

Jingyue Jia  1 , Suttinee Poolsup  2 , Jay E Salinas  2
Affiliations
Review

Cellular homeostatic responses to lysosomal damage

Jingyue Jia et al. Trends Cell Biol. 2025 Sep.

Abstract

Lysosomes are essential membrane-bound organelles that control cellular homeostasis by integrating intracellular functions with external signals. Their critical roles make lysosomal membranes vulnerable to rupture under various stressors, leading to cellular dysfunction. However, the mechanisms by which cells respond to lysosomal damage have only recently begun to be explored. In this review, we summarize the cellular mechanisms activated by lysosomal damage, emphasizing those that restore lysosomal integrity and sustain homeostasis, including recognition, repair, removal, replacement, and remodeling. Drawing on our expertise, we provide an in-depth focus on the remodeling process involved in these responses, including metabolic signaling and stress granule formation. Finally, we discuss the implications of lysosomal damage in human diseases, underscoring potential therapeutic strategies to preserve lysosomal function and alleviate related disorders.

Keywords: damaged lysosomes; recognition; remodeling; removal; repair; replacement.

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Conflict of interest statement

Declaration of interests The authors declare no conflict of interest

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