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Resources » Paper

Luke CJ et al. (2022) Commun Biol "Lysoptosis is an evolutionarily conserved cell death pathway moderated by intracellular serpins."

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  • Comments on Luke CJ et al. (2022) Commun Biol "Lysoptosis is an evolutionarily conserved cell death pathway moderated by intracellular serpins." (0)

  • Overview

    PMID:
    35022507
    DOI:
    10.1038/s42003-021-02953-x
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00062632

    Luke CJ, Markovina S, Good M, Wight IE, Thomas BJ, Linneman JM, Lanik WE, Koroleva O, Coffman MR, Miedel MT, Gong Q, Andress A, Campos Guerrero M, Wang S, Chen L, Beatty WL, Hausmann KN, White FV, Fitzpatrick JAJ, Orvedahl A, Pak SC, & Silverman GA (2022). Lysoptosis is an evolutionarily conserved cell death pathway moderated by intracellular serpins. Commun Biol, 5, 47. doi:10.1038/s42003-021-02953-x

    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.

    Authors: Luke CJ, Markovina S, Good M, Wight IE, Thomas BJ, Linneman JM, Lanik WE, Koroleva O, Coffman MR, Miedel MT, Gong Q, Andress A, Campos Guerrero M, Wang S, Chen L, Beatty WL, Hausmann KN, White FV, Fitzpatrick JAJ, Orvedahl A, Pak SC, Silverman GA


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