Control of mitosis, inflammation, and cell motility by limited leakage of lysosomes

Abstract

Lysosomal membrane permeabilization and subsequent leakage of lysosomal hydrolases into the cytosol are considered as the major hallmarks of evolutionarily conserved lysosome-dependent cell death. Contradicting this postulate, new sensitive methods that can detect a minimal lysosomal membrane damage have demonstrated that lysosomal leakage does not necessarily equal cell death. Notably, cells are not only able to survive minor lysosomal membrane permeabilization, but some of their normal functions actually depend on leaked lysosomal hydrolases. Here we discuss emerging data suggesting that spatially and temporally controlled lysosomal leakage delivers lysosomal hydrolases to specific subcellular sites of action and controls at least three essential cellular processes, namely mitotic chromosome segregation, inflammatory signaling, and cellular motility.

Keywords: Adhesion; Cathepsins; Chromosome segregation; Inflammation; Lysosomal membrane permeabilization; Lysosomal storage disorders; Lysosome; Mitosis; Motility; NLRP3 inflammasome.