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- Title
Lysoptosis is an evolutionarily conserved cell death pathway moderated by intracellular serpins.
- Authors
Luke, Cliff J.; Markovina, Stephanie; Good, Misty; Wight, Ira E.; Thomas, Brian J.; Linneman, John M.; Lanik, Wyatt E.; Koroleva, Olga; Coffman, Maggie R.; Miedel, Mark T.; Gong, Qingqing; Andress, Arlise; Campos Guerrero, Marlene; Wang, Songyan; Chen, LiYun; Beatty, Wandy L.; Hausmann, Kelsey N.; White, Frances V.; Fitzpatrick, James A. J.; Orvedahl, Anthony
- Abstract
Lysosomal membrane permeabilization (LMP) and cathepsin release typifies lysosome-dependent cell death (LDCD). However, LMP occurs in most regulated cell death programs suggesting LDCD is not an independent cell death pathway, but is conscripted to facilitate the final cellular demise by other cell death routines. Previously, we demonstrated that Caenorhabditis elegans (C. elegans) null for a cysteine protease inhibitor, srp-6, undergo a specific LDCD pathway characterized by LMP and cathepsin-dependent cytoplasmic proteolysis. We designated this cell death routine, lysoptosis, to distinguish it from other pathways employing LMP. In this study, mouse and human epithelial cells lacking srp-6 homologues, mSerpinb3a and SERPINB3, respectively, demonstrated a lysoptosis phenotype distinct from other cell death pathways. Like in C. elegans, this pathway depended on LMP and released cathepsins, predominantly cathepsin L. These studies suggested that lysoptosis is an evolutionarily-conserved eukaryotic LDCD that predominates in the absence of neutralizing endogenous inhibitors. Cliff Luke et al. report that lysoptosis is a eukaryotic stand-alone regulated cell death pathway. They identify that this new cell death modality predominates in the absence of neutralizing endogenous inhibitors.
- Subjects
CELL death; CYSTEINE proteinase inhibitors; SERPINS; EPITHELIAL cells; CAENORHABDITIS elegans
- Publication
Communications Biology, 2022, Vol 5, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-021-02953-x