4.5 Review

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

Journal

CURRENT OPINION IN CELL BIOLOGY
Volume 71, Issue -, Pages 29-37

Publisher

CURRENT BIOLOGY LTD
DOI: 10.1016/j.ceb.2021.02.003

Keywords

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

Categories

Funding

  1. Danish National Research Foundation [DNRF125]
  2. European Research Council [AdG340751]
  3. Danish Cancer Society [R90A5783, R269-A15695]
  4. Novo Nordisk Foundation [NNF15OC0018914]
  5. Danish Council for Independent Research [7016-00360]

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Recent research has shown that cells can survive even minor lysosomal membrane damage, and some normal functions depend on leaked lysosomal hydrolases. Spatially and temporally controlled lysosomal leakage can affect three essential cellular processes, including mitotic chromosome segregation, inflammatory signaling, and cellular motility.
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.

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