IRGM1 links mitochondrial quality control to autoimmunity.

Animals Autoimmune Diseases / genetics Autoimmunity Cells, Cultured Fibroblasts / immunology GTP-Binding Proteins / deficiency Gene Expression Regulation Macrophages / immunology Membrane Glycoproteins / genetics Membrane Proteins / genetics Mice, Inbred C57BL Mitochondria / genetics Mitophagy Nucleotidyltransferases / genetics Signal Transduction Toll-Like Receptor 7 / genetics

Journal

Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354

Informations de publication

Date de publication:
03 2021
Historique:
received: 27 08 2019
accepted: 18 12 2020
pubmed: 30 1 2021
medline: 27 4 2021
entrez: 29 1 2021
Statut: ppublish

Résumé

Mitochondrial abnormalities have been noted in lupus, but the causes and consequences remain obscure. Autophagy-related genes ATG5, ATG7 and IRGM have been previously implicated in autoimmune disease. We reasoned that failure to clear defective mitochondria via mitophagy might be a foundational driver in autoimmunity by licensing mitochondrial DNA-dependent induction of type I interferon. Here, we show that mice lacking the GTPase IRGM1 (IRGM homolog) exhibited a type I interferonopathy with autoimmune features. Irgm1 deletion impaired the execution of mitophagy with cell-specific consequences. In fibroblasts, mitochondrial DNA soiling of the cytosol induced cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-dependent type I interferon, whereas in macrophages, lysosomal Toll-like receptor 7 was activated. In vivo, Irgm1

Identifiants

DOI: 10.1038/s41590-020-00859-0 PMID: 33510463 PMC: PMC7906953
pubmed: 33510463
doi: 10.1038/s41590-020-00859-0
pii: 10.1038/s41590-020-00859-0
pmc: PMC7906953
mid: NIHMS1656423
doi:

Substances chimiques

Ifi1 protein, mouse 0
Membrane Glycoproteins 0
Membrane Proteins 0
Sting1 protein, mouse 0
Tlr7 protein, mouse 0
Toll-Like Receptor 7 0
Nucleotidyltransferases EC 2.7.7.-
cGAS protein, mouse EC 2.7.7.-
GTP-Binding Proteins EC 3.6.1.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

312-321

Subventions

Organisme : Intramural NIH HHS
ID : Z01 ES102005
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA ES103286
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI135398
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG060456
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI145929
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI148243
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG063373
Pays : United States

Commentaires et corrections

Type : CommentIn

Références

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Auteurs

Prashant Rai (P)

Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA. prashant.rai@nih.gov.
ORCID: 0000-0003-0258-4567

Kyathanahalli S Janardhan (KS)

Cellular & Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Integrated Laboratory Systems, Inc., Research Triangle Park, NC, USA.

Julie Meacham (J)

Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.

Jennifer H Madenspacher (JH)

Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.

Wan-Chi Lin (WC)

Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.

Peer W F Karmaus (PWF)

Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.

Jennifer Martinez (J)

Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.

Quan-Zhen Li (QZ)

Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Mei Yan (M)

Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Jialiu Zeng (J)

Department of Biomedical Engineering, Boston University, Boston, MA, USA.
ORCID: 0000-0001-7802-1432

Mark W Grinstaff (MW)

Department of Biomedical Engineering, Boston University, Boston, MA, USA.

Orian S Shirihai (OS)

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
ORCID: 0000-0001-8466-3431

Gregory A Taylor (GA)

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.
Department of Immunology, Duke University Medical Center, Durham, NC, USA.
Division of Geriatrics, Department of Medicine, Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC, USA.
Geriatric Research, Education, and Clinical Center, VA Medical Center, Durham, NC, USA.

Michael B Fessler (MB)

Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA. fesslerm@niehs.nih.gov.
ORCID: 0000-0002-8262-8613

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Auto-immunité › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Cellules › Cellules cultivées › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines G › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Glycoprotéines membranaires › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Renouvellement des mitochondries › Dégradation des mitochondries › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Nucleotidyltransferases › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › IRGM1 links mitochondrial quality control to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs de reconnaissance de motifs moléculaires › Récepteurs de type Toll › Récepteur de type Toll-7 › IRGM1 links mitochondrial quality control to...