RESOURCE TYPE,RESOURCE NAME,SOURCE,IDENTIFIER,NEW/REUSE,ADDITIONAL INFORMATION Dataset,Raw RNA-Seq data,Gene Expression Omnibus (GEO),GSE301127,New, Dataset,genome-wide CRISPR knockout screen,Zenodo,10.5281/zenodo.17180353,New,supplementary table 1 Dataset,RNAseq Dataset,Zenodo,10.5281/zenodo.17180353,New,supplementary table 2 Dataset,Differential gene score,Zenodo,10.5281/zenodo.17180353,New,"Cleaned tabular data Fig 1F, 1G, 5B, 5C" Dataset,Rstudio Code,Zenodo,10.5281/zenodo.17180353,New, Dataset,Cell viability assay,Zenodo,10.5281/zenodo.17180353,New,"Cleaned tabular data Fig 1B, 1C, 2B, 6C, Sfig 1D, Sfig 3B" Dataset,Cell death quantification (sytox green),Zenodo,10.5281/zenodo.17180353,New,"Cleaned tabular data Fig 1L, 2D, 5D, 7B, 7D, 7L, 8D, 8I" Dataset,Immunofluorescence quantification,Zenodo,10.5281/zenodo.17180353,New,"Cleaned tabular data Fig 2G, 2I, 2J, 3B, 3C, 3E, 4B, 4C, 5F, 5H, 5I, 6B, 6E, 6F, 6I, 6J, 6L, 7F, 8B, 8F, Sfig 4A, Sfig 5C prime" Dataset,Raw qPCR data,Zenodo,10.5281/zenodo.17180353,New, Dataset,qPCR quantification,Zenodo,10.5281/zenodo.17180353,New,"Cleaned tabular data Fig 1H, 2C, 6H, 7J, SFig 1C, SFig 8C" Dataset,ELISA quantification,Zenodo,10.5281/zenodo.17180353,New,"Cleaned tabular data Fig 1I, 7H" Dataset,Immunoblots,Zenodo,10.5281/zenodo.17180353,New,"Fig 1A,1C,1J, 2E,2K, 6L,6M, 7A,7G,7K, S1B,S1E, S2A, S3A, S3C, S5A,S5B, S6, S7" Dataset,Live cell videos,Zenodo,10.5281/zenodo.17180353,New,"Fig 3A, 4D, 4E, 6G" Software/code,Xcalibr ,https://www.thermofisher.com/order/catalog/product/OPTON-30965,,Reuse, Software/code,MAGeCK,"https://sourceforge.net/p/mageck/wiki/Home/ https://sourceforge.net/p/mageck/wiki/Home/",RRID:SCR_025016,Reuse,version 0.5.8 Software/code,Rstudio ," https://posit.co/",RRID:SCR_000432,Reuse,version: 4.1.2 Software/code,Prism10,http://www.graphpad.com/,RRID:SCR_002798,Reuse, Software/code,MetaMorph,http://www.moleculardevices.com/Products/Software/Meta-Imaging-Series/MetaMorph.html,RRID:SCR_002368,Reuse, Software/code,FIJI Image J ,https://imagej.net/,RRID:SCR_003070,Reuse, Software/code,Galaxy platform,http://galaxyproject.org/ ,RRID:SCR_006281,Reuse, Software/code,Trimomatics,http://www.usadellab.org/cms/?page=trimmomatic,RRID:SCR_011848,Reuse,version: v0.39 Software/code,DeSeq2,https://bioconductor.org/packages/release/bioc/html/DESeq2.html,RRID:SCR_015687,Reuse,version: 1.34.0 Software/code,ComplexHeatmaps,https://bioconductor.org/packages/release/bioc/html/ComplexHeatmap.html ,RRID:SCR_017270,Reuse, Software/code,HISAT2,http://ccb.jhu.edu/software/hisat2/index.shtml ,RRID:SCR_015530,Reuse, Software/code,featureCounts,http://bioinf.wehi.edu.au/featureCounts/ ,RRID:SCR_012919,Reuse, Software/code,SAMtools,http://htslib.org/,RRID:SCR_002105,Reuse,Galaxy Version 2.0.5 Software/code,WashU Epigenome Browser,http://epigenomegateway.wustl.edu/,RRID:SCR_006208,Reuse, Protocol,Culturing of cell lines,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,Isolation and culturing of bone-marrow derived macrophages (BMDMs),protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,Transfection and generation of stable cell lines,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,RNA interference,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,"Cells lysates, PAGE and immunoblotting",protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,Blue native PAGE to evaluate NLRP3 oligomer ,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,Pyroptotic cell death assay,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,Preparation of adenovirus and infection of cells,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,Pooled genome-wide CRISPR knockout screen,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,Immunofluorescence and image acquisition,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,Live cell microscopy,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,Image processing and quantification,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,RNA isolation and qPCR,Institute for Research in Immunology and Cancer (IRIC),https://www.iric.ca/en/research/platforms-and-infrastructures,Reuse, Protocol,Transmission electron microscopy,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,Immunoisolation of lysosomes,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,Isolation of cytosolic fractions for mtDNA qPCR,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,Detection of extracellular cytokine,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Protocol,RNA-Seq,Institute for Research in Immunology and Cancer (IRIC),https://www.iric.ca/en/research/platforms-and-infrastructures,Reuse, Protocol,PCR validation of Rho0 cells,protocols.io,dx.doi.org/10.17504/protocols.io.8epv5x266g1b/v2,New, Antibody,Actin,Sigma,"Cat# A2228, RRID:AB_476697",Reuse, Antibody,AIF(E1),Santa Cruz Biotechnology,"Cat# sc-13116, RRID:AB_626654",Reuse, Antibody,Caspase 1,Adipogen,"Cat# AG-20B-0042, RRID:AB_2490248",Reuse, Antibody,Cleaved caspase 3,Cell Signaling,"Cat# 9661, RRID:AB_2341188",Reuse, Antibody,Cleaved caspase 7,Cell Signaling,"Cat# 9491, RRID:AB_2068144",Reuse, Antibody,cGAS,Cell Signaling Technology," Cat# 15102, RRID:AB_2732795",Reuse, Antibody,FLAG,Sigma,"Cat# F1804, RRID:AB_262044",Reuse, Antibody,GSDMD,Abcam,"Cat# ab210070, RRID:AB_2893325",Reuse, Antibody,GSDME,Abcam,"Cat# ab215191, RRID:AB_2737000",Reuse, Antibody,Histone 3,Abclonal,"Cat# A2348, RRID:AB_2631273",Reuse, Antibody,HA,Sigma,"Cat# H9658, RRID:AB_260092",Reuse, Antibody,IL1b,Bio-Techne,"Cat# AB-401-NA, RRID:AB_354347",Reuse, Antibody,LAMP1,Cell Signaling,"Cat# 9091, RRID:AB_2687579",Reuse, Antibody,LRRK2,Abcam,"Cat# ab133474, RRID:AB_2713963",Reuse, Antibody,MAPL,Sigma-Aldrich,"Cat# HPA017681, RRID:AB_1848699",Reuse, Antibody,MFN2(XX-1),Santa Cruz,"Cat# sc-100560, RRID:AB_2235195",Reuse, Antibody,NLRP3,Cell Signaling,"Cat# 15101, RRID:AB_2722591",Reuse, Antibody,PMP70,Abcam,"Cat# ab3421, RRID:AB_2219901",Reuse, Antibody,RHOT1,Sigma-Aldrich,"Cat# HPA010687, RRID:AB_1079813",Reuse, Antibody,TOM20,Sigma-Aldrich,"Cat# HPA011562, RRID:AB_1080326",Reuse, Antibody,UQCR2,Proteintech,"Cat# 83667-2-RR, RRID:AB_3671273",Reuse, Antibody,Vinculin,Sigma-Aldrich,"Cat# V4505, RRID:AB_477617",Reuse, Antibody,VPS35,Abnova,"Cat# H00055737-M02, RRID:AB_566269",Reuse, Antibody,Complex I,Abcam,"Cat# ab109798, RRID:AB_10862214",Reuse, Antibody,dsDNA,Abcam,"Cat# ab27156, RRID:AB_470907",Reuse, Antibody,pStat3,Abclonal,"Cat# AP0474, RRID:AB_2771567",Reuse, Antibody,NF-kB p65,Abcam,"Cat# ab16502, RRID:AB_443394",Reuse, Antibody,TOM40,Proteintech,"Cat# 18409-1-AP, RRID:AB_2303725",Reuse, Antibody,HRP-anti-mouse,Cytiva,"Cat# NA931, RRID:AB_772210",Reuse, Antibody,HRP-anti-rabbit,Cytiva,"Cat# NA934, RRID:AB_772206",Reuse, Antibody,Mouse IgG Alexafluor 568,Invitrogen,"Cat# A-11031, RRID:AB_144696",Reuse, Antibody,Mouse IgG Alexafluor 488,Invitrogen,"Cat# A-11029, RRID:AB_2534088",Reuse, Antibody,Mouse IgG2a Alexafluor 488,Invitrogen,"Cat# A-21131, RRID:AB_2535771",Reuse, Antibody,Mouse IgG2b Alexfluor 594,Invitrogen,"Cat# A-21145, RRID:AB_2535781",Reuse, Antibody,Mouse IgG Alexafluor 647,Invitrogen,"Cat# A-21235, RRID:AB_2535804",Reuse, Antibody,Rabbit IgG Alexafluor 647,Invitrogen,"Cat# A-21244, RRID:AB_2535812",Reuse, Antibody,MitoTracker Deep Red FM,Invitrogen,M22526,Reuse, Antibody,LysoTracker Red FM,Invitrogen,L7528,Reuse, Antibody,Dextran Alex Fluor 555,Invitrogen,D34679,Reuse, "Chemical, peptide, or recombinant protein",DAPI,Invitrogen,D1306,Reuse, "Chemical, peptide, or recombinant protein",pan-caspase inhibitor ZVAD,Enzo Life ,ALX-260-020,Reuse, "Chemical, peptide, or recombinant protein",LPS Ultrapure from E. coli O111:B4,InvivoGen,tlrl-3pelps,Reuse, "Chemical, peptide, or recombinant protein",INFg,Peprotech,315-05,Reuse, "Chemical, peptide, or recombinant protein",2' 3'cGAMP,InvivoGen,tlrl-nacga23-02,Reuse, "Chemical, peptide, or recombinant protein",CASP1i (Ac-YVAD-cmk),InvivoGen,inh-yvad,Reuse, "Chemical, peptide, or recombinant protein",NLRP3i MCC950,InvivoGen,ihn-mcc,Reuse, "Chemical, peptide, or recombinant protein",cGASi,InvivoGen,inh-g140,Reuse, "Chemical, peptide, or recombinant protein",STING1i (H-151),InvivoGen,inh-h151,Reuse, "Chemical, peptide, or recombinant protein",Lipofectamine 2000,ThermoFisher,11668019,Reuse, "Chemical, peptide, or recombinant protein",Lipofectamine RNAiMAX,Invitrogen,13778150,Reuse, Critical commercial assay,RNeasy Mini Kit,Qiagen,71404,Reuse, Critical commercial assay,MycoAlert mycoplasma detection kit,Lonza,LT07-418,Reuse, Critical commercial assay,"Promega CellTiter-Glo® 2.0 Luminescence Cell 835 Viability Assay kit",Promega,G9241,Reuse, Critical commercial assay,Bradford assay ,Bio-Rad,Cat# 5000006EDU,Reuse, Critical commercial assay,Western-Lightning PLUS-ECL,Perkin-Elmer,NEL105001EA,Reuse, Critical commercial assay,SYTOX Green ,Invitrogen,S7020,Reuse, Critical commercial assay,High Pure PCR Template Preparation Kit,Roche,11732668001,Reuse, Critical commercial assay,Quant-iTTM PicoGreenTM dsDNA Assay,ThermoFisher Scientific,P7581,Reuse, Critical commercial assay,SYBR Green Supermix,Biorad,1725271,Reuse, Critical commercial assay,IL-1b Duoset ELISA,R&D Systems ,DY401-05,Reuse, Critical commercial assay,Nucleospin,Takara,704955.5,Reuse, Experimental model: Cell line,U2OS,ATCC U-2 OS - HTB-96,RRID:CVCL_0042,Reuse, Experimental model: Cell line,human fibroblasts,"Gift from E. Shoubridge, MNI",McGill University,Reuse, Experimental model: Cell line,HUH-7,"Gift from E. Shoubridge, Mcgill University",RRID:CVCL_0336,Reuse, Experimental model: Cell line,baby mouse kidney [BMK] cells,"Gordon Charles Shore, McGill University",,Reuse, Experimental model: Cell line,wild type 143b cells,"Gift from E. Shoubridge, Mcgill University",,Reuse, Experimental model: Cell line,Rho0 143b cells,"Gift from E. Shoubridge, Mcgill University",RRID:CVCL_ZL52,Reuse, Experimental model: Cell line,Ad-293 cells,Agilent,"Cat# 240085, RRID:CVCL_9804",Reuse, Experimental model: Cell line,U2OS TMEM192-3xHA,"McBride lab, McGill University",RRID:CVCL_F0QI,New, Experimental model: Cell line,U2OS RFP-Gal3,"McBride lab, McGill University",RRID: CVCL_F0QJ,New, Experimental model: Cell line,U2OS Parkin-GFP,"Gift from Edward Fon, McGill University", RRID:CVCL_F0QH,New, Experimental model: Organism/strain,MAPL KO mouse,McBride lab,RRID:MGI:7524577,New, Experimental model: Organism/strain,LRRK2 KO mouse,The Jackson Laboratories,RRID:IMSR_JAX:012444,Reuse, Experimental model: Organism/strain,C57BL/6J,The Jackson Laboratories,RRID:MGI:7524577,Reuse, Lentivirus,"CRISPR 862 Brunello lentiviral pooled library ",Addgene #73178 ; http://n2t.net/addgene:73178,RRID:Addgene_73178,Reuse, Adenovirus,Ad-FLAG-MAPL,Vector Biosystems,custom made,New, Adenovirus,Ad-rtTA,"Gordon Charles Shore, McGill University",,Reuse, Adenovirus,Ad-ΔRING-FLAG-MAPL,Vector Biosystems,custom made,New, Adenovirus,Ad-tBID,"Gordon Charles Shore, McGill University",,Reuse, Recombinant DNA,pmRFP-C1-Galectin-3,"Maximiliano Gutierrez, Francis Crick Institute",,Reuse, Recombinant DNA,pOCT-GFP,"Gift from J. Silvius, Mcgill University",,Reuse, Recombinant DNA,TMEM192-3xHA,Addgene,RRID:Addgene_102930,Reuse, Recombinant DNA,pcDNA3.1,ThermoFisher,V79020,Reuse, Oligonucleotide,cGAS/MB21D1,Dharmacon,L-015607-02,Reuse, Oligonucleotide,GSDMC,Dharmacon,L-014716-02,Reuse, Oligonucleotide,GSDMD,Dharmacon,L-016207-00,Reuse, Oligonucleotide,GSDME/DFNA5,Dharmacon,L-011844-00,Reuse, Oligonucleotide,LRRK2 ,Dharmacon,L-006323-00,Reuse, Oligonucleotide,MIRO1,Dharmacon,L-010365-01,Reuse, Oligonucleotide,MIRO2,Dharmacon,L-008340-01,Reuse, Oligonucleotide,VPS35,Dharmacon,J-010894-05,Reuse, Oligonucleotide (primer),NLRP3,,,Reuse,"forward-AAAGAGATGAGCCGAAGTGG, rev-ATCCACTCCTCTTCAATGCTG" Oligonucleotide (primer),IL1B,,,Reuse,"forw-TACCTGTCCTGCGTGTTGAA, rev-TCTTTGGGTAATTTTTGGGATCT" Oligonucleotide (primer),IL6,,,Reuse,"forw-GATGAGTACAAAAGTCCTGATCCA, rev-CTGCAGCCACTGGTTCTGT" Oligonucleotide (primer),IFNA4,,,Reuse,"forw-CTGGCACAAATGGGAAGAAT, rev-AACTCCTCCTCGGGGAATC" Oligonucleotide (primer),IFNB1,,,Reuse,"forw-CGACACTGTTCGTGTTGTCA, rev-GAAGCACAACAGGAGAGCAA" Oligonucleotide (primer),PPIA,,,Reuse,"forw-CCTAAAGCATACGGGTCCTG, rev-TTTCACTTTGCCAAACACCA" Oligonucleotide (primer),MT-ND1,,,Reuse,"forw-CCACCCTTATCACAACACAAGA, rev-TCATATTATGGCCAAGGGTCA" Oligonucleotide (primer),16S,,,Reuse, Oligonucleotide (primer),MT- CO1,,,Reuse,"forw-CGTTTCCCCGCATAAACAACA, rev-CCGGCCTCCACTATAGCAGA" Oligonucleotide (primer),MT-ND6,,,Reuse,"forw-ATTGGTGCTGTGGGTGAAA, rev-CCTGACCCCTCTCCTTCATA" Oligonucleotide (primer),TERT,,,Reuse,"forw-GAGGCCAGAGCAGTGAACA, rev-CAGACACTTCTCCCCATTGC" Equipment,Zeiss Axio Observer.Z1," https://www.zeiss.com/microscopy/us/products/light-microscopes/axio-observer-for-biology.html",RRID:SCR_021351,Reuse, Equipment,Olympus IX83 confocal microscope,https://evidentscientific.com/en/,,Reuse,