Lysoptosis is an Evolutionarily Conserved Cell Death Pathway Moderated by Intracellular Serpins

Overview

Journal Commun Biol

Specialty Biology

Date 2022 Jan 13

PMID 35022507

Authors

Cliff J Luke

Stephanie Markovina

Misty Good

Ira E Wight

Brian J Thomas

John M Linneman

Wyatt E Lanik

Olga Koroleva

Maggie R Coffman

Mark T Miedel

Qingqing Gong

Arlise Andress

Marlene Campos Guerrero

Songyan Wang

Liyun Chen

Wandy L Beatty

Kelsey N Hausmann

Frances V White

James A J Fitzpatrick

Anthony Orvedahl

Stephen C Pak

Gary A Silverman

Affiliations

Soon will be listed here.

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.

Citing Articles

An alveolus lung-on-a-chip model of lung infection.

Ektnitphong V, Dias B, Campos P, Shiloh M bioRxiv. 2024; .

PMID: 39257817 PMC: 11383683. DOI: 10.1101/2024.08.30.610530.

Therapeutic strategies of targeting non-apoptotic regulated cell death (RCD) with small-molecule compounds in cancer.

Jin X, Jin W, Tong L, Zhao J, Zhang L, Lin N Acta Pharm Sin B. 2024; 14(7):2815-2853.

PMID: 39027232 PMC: 11252466. DOI: 10.1016/j.apsb.2024.04.020.

Pharmacological inhibition of RUNX1 reduces infarct size after acute myocardial infarction in rats and underlying mechanism revealed by proteomics implicates repressed cathepsin levels.

Chen H, Wang S, Zhang X, Hua X, Liu M, Wang Y Funct Integr Genomics. 2024; 24(3):113.

PMID: 38862712 PMC: 11166773. DOI: 10.1007/s10142-024-01391-2.

Surveying the landscape of emerging and understudied cell death mechanisms.

Leak L, Dixon S Biochim Biophys Acta Mol Cell Res. 2023; 1870(3):119432.

PMID: 36690038 PMC: 9969746. DOI: 10.1016/j.bbamcr.2023.119432.

Alveolar cells in the mammary gland: lineage commitment and cell death.

Watson C Biochem J. 2022; 479(9):995-1006.

PMID: 35551601 PMC: 9162463. DOI: 10.1042/BCJ20210734.

References

Galluzzi L, Vitale I, Aaronson S, Abrams J, Adam D, Agostinis P . Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018; 25(3):486-541. PMC: 5864239. DOI: 10.1038/s41418-017-0012-4. View

Tang D, Kang R, Vanden Berghe T, Vandenabeele P, Kroemer G . The molecular machinery of regulated cell death. Cell Res. 2019; 29(5):347-364. PMC: 6796845. DOI: 10.1038/s41422-019-0164-5. View

Kreuzaler P, Staniszewska A, Li W, Omidvar N, Kedjouar B, Turkson J . Stat3 controls lysosomal-mediated cell death in vivo. Nat Cell Biol. 2011; 13(3):303-9. DOI: 10.1038/ncb2171. View

Sargeant T, Lloyd-Lewis B, Resemann H, Ramos-Montoya A, Skepper J, Watson C . Stat3 controls cell death during mammary gland involution by regulating uptake of milk fat globules and lysosomal membrane permeabilization. Nat Cell Biol. 2014; 16(11):1057-1068. PMC: 4216597. DOI: 10.1038/ncb3043. View

Lu K, Yamashita Y . Germ cell connectivity enhances cell death in response to DNA damage in the testis. Elife. 2017; 6. PMC: 5577909. DOI: 10.7554/eLife.27960. View

Yacobi-Sharon K, Namdar Y, Arama E . Alternative germ cell death pathway in Drosophila involves HtrA2/Omi, lysosomes, and a caspase-9 counterpart. Dev Cell. 2013; 25(1):29-42. DOI: 10.1016/j.devcel.2013.02.002. View

Wang F, Gomez-Sintes R, Boya P . Lysosomal membrane permeabilization and cell death. Traffic. 2018; 19(12):918-931. DOI: 10.1111/tra.12613. View

Mulay S, Honarpisheh M, Foresto-Neto O, Shi C, Desai J, Zhao Z . Mitochondria Permeability Transition versus Necroptosis in Oxalate-Induced AKI. J Am Soc Nephrol. 2019; 30(10):1857-1869. PMC: 6779355. DOI: 10.1681/ASN.2018121218. View

Zhao M, Antunes F, Eaton J, Brunk U . Lysosomal enzymes promote mitochondrial oxidant production, cytochrome c release and apoptosis. Eur J Biochem. 2003; 270(18):3778-86. DOI: 10.1046/j.1432-1033.2003.03765.x. View

10.

Gao H, Bai Y, Jia Y, Zhao Y, Kang R, Tang D . Ferroptosis is a lysosomal cell death process. Biochem Biophys Res Commun. 2018; 503(3):1550-1556. DOI: 10.1016/j.bbrc.2018.07.078. View

11.

Peri P, Nuutila K, Vuorinen T, Saukko P, Hukkanen V . Cathepsins are involved in virus-induced cell death in ICP4 and Us3 deletion mutant herpes simplex virus type 1-infected monocytic cells. J Gen Virol. 2010; 92(Pt 1):173-80. DOI: 10.1099/vir.0.025080-0. View

12.

Vanden Berghe T, Vanlangenakker N, Parthoens E, Deckers W, Devos M, Festjens N . Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features. Cell Death Differ. 2009; 17(6):922-30. DOI: 10.1038/cdd.2009.184. View

13.

Yashin D, Romanova E, Ivanova O, Sashchenko L . The Tag7-Hsp70 cytotoxic complex induces tumor cell necroptosis via permeabilisation of lysosomes and mitochondria. Biochimie. 2016; 123:32-6. DOI: 10.1016/j.biochi.2016.01.007. View

14.

Vanden Berghe T, Grootjans S, Goossens V, Dondelinger Y, Krysko D, Takahashi N . Determination of apoptotic and necrotic cell death in vitro and in vivo. Methods. 2013; 61(2):117-29. DOI: 10.1016/j.ymeth.2013.02.011. View

15.

KERR J, Wyllie A, Currie A . Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972; 26(4):239-57. PMC: 2008650. DOI: 10.1038/bjc.1972.33. View

16.

Aits S, Jaattela M . Lysosomal cell death at a glance. J Cell Sci. 2013; 126(Pt 9):1905-12. DOI: 10.1242/jcs.091181. View

17.

Majno G, Joris I . Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol. 1995; 146(1):3-15. PMC: 1870771. View

18.

Festjens N, Vanden Berghe T, Vandenabeele P . Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response. Biochim Biophys Acta. 2006; 1757(9-10):1371-87. DOI: 10.1016/j.bbabio.2006.06.014. View

19.

Grooten J, Goossens V, Vanhaesebroeck B, Fiers W . Cell membrane permeabilization and cellular collapse, followed by loss of dehydrogenase activity: early events in tumour necrosis factor-induced cytotoxicity. Cytokine. 1993; 5(6):546-55. DOI: 10.1016/s1043-4666(05)80003-1. View

20.

Schweichel J, Merker H . The morphology of various types of cell death in prenatal tissues. Teratology. 1973; 7(3):253-66. DOI: 10.1002/tera.1420070306. View