7e68a7ce0d05361f86f17f71bfcce70d ijmolsci_a2021v22n16p8523.pdf 43209b90eaea9fb81f05168d55702da03b76b1aa ijmolsci_a2021v22n16p8523.pdf 582b98ac52340d40a0d84fb804c34879a348f04170fb0855ddf72c92584f55c7 ijmolsci_a2021v22n16p8523.pdf Title: Mitochondria-Induced Immune Response as a Trigger for Neurodegeneration: A Pathogen from Within Subject: Symbiosis between the mitochondrion and the ancestor of the eukaryotic cell allowed cellular complexity and supported life. Mitochondria have specialized in many key functions ensuring cell homeostasis and survival. Thus, proper communication between mitochondria and cell nucleus is paramount for cellular health. However, due to their archaebacterial origin, mitochondria possess a high immunogenic potential. Indeed, mitochondria have been identified as an intracellular source of molecules that can elicit cellular responses to pathogens. Compromised mitochondrial integrity leads to release of mitochondrial content into the cytosol, which triggers an unwanted cellular immune response. Mitochondrial nucleic acids (mtDNA and mtRNA) can interact with the same cytoplasmic sensors that are specialized in recognizing genetic material from pathogens. High-energy demanding cells, such as neurons, are highly affected by deficits in mitochondrial function. Notably, mitochondrial dysfunction, neurodegeneration, and chronic inflammation are concurrent events in many severe debilitating disorders. Interestingly in this context of pathology, increasing number of studies have detected immune-activating mtDNA and mtRNA that induce an aberrant production of pro-inflammatory cytokines and interferon effectors. Thus, this review provides new insights on mitochondria-driven inflammation as a potential therapeutic target for neurodegenerative and primary mitochondrial diseases. Keywords: mtDNA; mtRNA; mitochondrial dysfunction; mitochondrial disorders; neurodegeneration; antiviral response; inflammation; innate immunity; interferon Author: Marta Luna-Sánchez, Patrizia Bianchi and Albert Quintana Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Aug 10 06:03:01 2021 CEST ModDate: Tue Aug 10 06:29:38 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 19 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2010124 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 10 0 PMUDPX+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 UBUEOD+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 DTOVWA+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 AIQCCL+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 36 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 39 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 56 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 60 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 64 0 UUQNXZ+EURM10 Type 1 Builtin yes yes no 80 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 88 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 92 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 96 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 100 0 FXXUVH+CMSY10 Type 1 Builtin yes yes no 111 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 122 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 126 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 130 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 134 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 165 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 169 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 173 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 177 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 197 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 201 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 205 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-03-10 03:01:39 CET RepresentationInformation: ijmolsci_a2021v22n16p8523.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-03-08 11:14:40 CET Size: 2010124 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 587 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Mitochondria in the Eukaryotic Cell: A Double-Edged Sword Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: mtDNA and the Immune System: Keeping Your Friend Close and Your Enemy Closer Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Innate Immune Sensors and mtDNA: To Detect and to “Protect”? Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: mtDNA Mitochondrial Escape: A Double-Membrane Prison Break Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Mitochondrial Dysfunction and mtDNA Release: A Crossline between Health and Disease Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Mitochondrial RNA: A New Villain in Town Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Concluding Remarks: PAMP-Ing the Cell up Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Info: Title: Mitochondria-Induced Immune Response as a Trigger for Neurodegeneration: A Pathogen from Within Author: Marta Luna-Sánchez, Patrizia Bianchi and Albert Quintana Subject: Symbiosis between the mitochondrion and the ancestor of the eukaryotic cell allowed cellular complexity and supported life. Mitochondria have specialized in many key functions ensuring cell homeostasis and survival. Thus, proper communication between mitochondria and cell nucleus is paramount for cellular health. However, due to their archaebacterial origin, mitochondria possess a high immunogenic potential. Indeed, mitochondria have been identified as an intracellular source of molecules that can elicit cellular responses to pathogens. Compromised mitochondrial integrity leads to release of mitochondrial content into the cytosol, which triggers an unwanted cellular immune response. Mitochondrial nucleic acids (mtDNA and mtRNA) can interact with the same cytoplasmic sensors that are specialized in recognizing genetic material from pathogens. High-energy demanding cells, such as neurons, are highly affected by deficits in mitochondrial function. Notably, mitochondrial dysfunction, neurodegeneration, and chronic inflammation are concurrent events in many severe debilitating disorders. Interestingly in this context of pathology, increasing number of studies have detected immune-activating mtDNA and mtRNA that induce an aberrant production of pro-inflammatory cytokines and interferon effectors. Thus, this review provides new insights on mitochondria-driven inflammation as a potential therapeutic target for neurodegenerative and primary mitochondrial diseases. 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Annotation: Subtype: Link Rect: 358, 341, 395, 352 Annotation: Subtype: Link Rect: 316, 307, 354, 318 Annotation: Subtype: Link Rect: 99, 273, 137, 283 Annotation: Subtype: Link Rect: 104, 238, 142, 249 Annotation: Subtype: Link Rect: 148, 238, 184, 249 Annotation: Subtype: Link Rect: 466, 226, 504, 237 Annotation: Subtype: Link Rect: 510, 226, 546, 237 Annotation: Subtype: Link Rect: 454, 203, 492, 214 Annotation: Subtype: Link Rect: 520, 192, 557, 203 Annotation: Subtype: Link Rect: 491, 180, 528, 191 Annotation: Subtype: Link Rect: 462, 157, 499, 168 Annotation: Subtype: Link Rect: 502, 146, 539, 157 Annotation: Subtype: Link Rect: 516, 134, 553, 145 Annotation: Subtype: Link Rect: 95, 112, 132, 122 Annotation: Subtype: Link Rect: 139, 112, 175, 122 Annotation: Subtype: Link Rect: 491, 88, 529, 99 Page: Sequence: 19 Annotations: Annotation: Subtype: Link Rect: 369, 721, 407, 732 Annotation: Subtype: Link Rect: 415, 698, 453, 709 Annotation: Subtype: Link Rect: 459, 698, 495, 709 Annotation: Subtype: Link Rect: 113, 664, 150, 674 Annotation: Subtype: Link Rect: 437, 640, 474, 651 Annotation: Subtype: Link Rect: 244, 618, 281, 628 Annotation: Subtype: Link Rect: 310, 594, 347, 605 Checksum: c3ecef42 Type: CRC32 Checksum: 7e68a7ce0d05361f86f17f71bfcce70d Type: MD5 Checksum: 43209b90eaea9fb81f05168d55702da03b76b1aa Type: SHA-1