Mild mitochondrial impairment enhances innate immunity and longevity through ATFS-1 and p38 signaling.
C. elegans
aging
innate immunity
mitochondria
mitochondrial unfolded protein response
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 12 2021
06 12 2021
Historique:
revised:
10
09
2021
received:
29
03
2021
accepted:
17
09
2021
pubmed:
8
10
2021
medline:
15
3
2022
entrez:
7
10
2021
Statut:
ppublish
Résumé
While mitochondrial function is essential for life in all multicellular organisms, a mild impairment of mitochondrial function can extend longevity in model organisms. By understanding the molecular mechanisms involved, these pathways might be targeted to promote healthy aging. In studying two long-lived mitochondrial mutants in C. elegans, we found that disrupting subunits of the mitochondrial electron transport chain results in upregulation of genes involved in innate immunity, which is driven by the mitochondrial unfolded protein response (mitoUPR) but also dependent on the canonical p38-mediated innate immune signaling pathway. Both of these pathways are required for the increased resistance to bacterial pathogens and extended longevity of the long-lived mitochondrial mutants, as is the FOXO transcription factor DAF-16. This work demonstrates that both the p38-mediated innate immune signaling pathway and the mitoUPR act in concert on the same innate immunity genes to promote pathogen resistance and longevity and that input from the mitochondria can extend longevity by signaling through these pathways. This indicates that multiple evolutionarily conserved genetic pathways controlling innate immunity also function to modulate lifespan.
Identifiants
pubmed: 34617666
doi: 10.15252/embr.202152964
pmc: PMC8647147
doi:
Substances chimiques
Caenorhabditis elegans Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e52964Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM121756
Pays : United States
Organisme : CIHR
ID : 399148
Pays : Canada
Organisme : NIH HHS
ID : P40 OD010440
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG054215
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK036836
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122610
Pays : United States
Organisme : CIHR
ID : 416150
Pays : Canada
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
Références
Mech Ageing Dev. 1977 Nov-Dec;6(6):413-29
pubmed: 926867
Nat Rev Genet. 2001 Apr;2(4):256-67
pubmed: 11283698
Science. 2003 Jun 20;300(5627):1921
pubmed: 12817143
PLoS Genet. 2018 Mar 9;14(3):e1007268
pubmed: 29522556
Cell. 2013 Aug 1;154(3):676-690
pubmed: 23911329
Mech Ageing Dev. 2011 Oct;132(10):519-21
pubmed: 21893079
WormBook. 2018 Aug 14;2018:1-35
pubmed: 26694508
EMBO J. 2017 Apr 13;36(8):1046-1065
pubmed: 28283579
Nature. 2010 Mar 25;464(7288):504-12
pubmed: 20336132
Nature. 2003 Jul 17;424(6946):277-83
pubmed: 12845331
Aging Cell. 2010 Jun;9(3):433-47
pubmed: 20346072
J Gerontol A Biol Sci Med Sci. 2019 Jul 12;74(8):1206-1214
pubmed: 30247515
Nat Rev Immunol. 2010 Jan;10(1):47-58
pubmed: 20029447
PLoS Genet. 2014 Feb 27;10(2):e1004097
pubmed: 24586177
Free Radic Biol Med. 2017 Jul;108:362-373
pubmed: 28392283
Cell Metab. 2012 Apr 4;15(4):451-65
pubmed: 22482728
PLoS Genet. 2015 May 27;11(5):e1005265
pubmed: 26016853
Cell. 2006 Mar 10;124(5):1055-68
pubmed: 16530050
Nature. 1999 Dec 16;402(6763):804-9
pubmed: 10617200
Cell. 2014 Nov 6;159(4):709-13
pubmed: 25417146
Cell Rep. 2016 Aug 30;16(9):2399-414
pubmed: 27545884
Nature. 2007 Feb 22;445(7130):922-6
pubmed: 17277769
Genome Biol. 2014;15(12):550
pubmed: 25516281
PLoS Genet. 2010 Apr 01;6(4):e1000892
pubmed: 20369020
BMC Biol. 2018 Dec 18;16(1):147
pubmed: 30563508
EMBO Rep. 2021 Dec 6;22(12):e52964
pubmed: 34617666
Science. 1999 May 21;284(5418):1313-8
pubmed: 10334979
Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):E4458-67
pubmed: 25288734
Mol Cell. 2016 Aug 18;63(4):553-566
pubmed: 27540856
Nat Commun. 2017 Dec 12;8(1):2063
pubmed: 29234056
PLoS Genet. 2019 Feb 21;15(2):e1007830
pubmed: 30789901
PLoS Genet. 2015 Feb 11;11(2):e1004972
pubmed: 25671321
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2408-13
pubmed: 10051655
J Exp Biol. 2014 Jan 1;217(Pt 1):137-43
pubmed: 24353213
Nat Genet. 2003 Jan;33(1):40-8
pubmed: 12447374
Neurobiol Dis. 2016 Dec;96:1-11
pubmed: 27544481
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):715-20
pubmed: 9892699
Methods Mol Biol. 2014;1149:653-69
pubmed: 24818940
Nature. 2003 Jan 9;421(6919):182-7
pubmed: 12483226
Nature. 1993 Dec 2;366(6454):461-4
pubmed: 8247153
Hum Mol Genet. 2007 Feb 15;16(4):431-44
pubmed: 17210671
Genetics. 2002 Jul;161(3):1101-12
pubmed: 12136014
Genes Dev. 2005 Oct 1;19(19):2278-83
pubmed: 16166371
PLoS Biol. 2010 Dec 07;8(12):e1000556
pubmed: 21151885
Curr Biol. 2009 Oct 13;19(19):1591-8
pubmed: 19747824
Genetics. 1995 Mar;139(3):1247-59
pubmed: 7768437
F1000Res. 2015 Dec 30;4:1521
pubmed: 26925227
Science. 2002 Dec 20;298(5602):2398-401
pubmed: 12471266
Annu Rev Med. 2018 Jan 29;69:437-449
pubmed: 29106805
Life Sci Alliance. 2021 Sep 28;4(12):
pubmed: 34583931
Genetics. 2000 Apr;154(4):1597-610
pubmed: 10747056
Nat Rev Immunol. 2014 Jul;14(7):463-77
pubmed: 24962261
Science. 2002 Jul 26;297(5581):623-6
pubmed: 12142542
Mech Ageing Dev. 2007 Jan;128(1):92-105
pubmed: 17116321
Cell Metab. 2019 May 7;29(5):1192-1205.e8
pubmed: 30905669
Science. 2001 Apr 6;292(5514):104-6
pubmed: 11292874
PLoS Biol. 2011 Jun;9(6):e1001084
pubmed: 21713031
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Mol Cell. 2015 Apr 2;58(1):123-33
pubmed: 25773600
PLoS Genet. 2016 Jul 15;12(7):e1006133
pubmed: 27420916
Nature. 2014 Dec 18;516(7531):414-7
pubmed: 25274306
PLoS Genet. 2011 May;7(5):e1002082
pubmed: 21625567
Science. 2012 Aug 3;337(6094):587-90
pubmed: 22700657
Science. 1996 May 17;272(5264):1010-3
pubmed: 8638122
Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5785-90
pubmed: 22451939
Cell. 2014 May 8;157(4):897-909
pubmed: 24813612
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
Aging Cell. 2014 Dec;13(6):1075-85
pubmed: 25257342
PLoS Genet. 2006 Nov 10;2(11):e183
pubmed: 17096597
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):5981-6
pubmed: 23530189
Dev Cell. 2001 Nov;1(5):633-44
pubmed: 11709184
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W202-8
pubmed: 19458158
Aging (Albany NY). 2016 Apr;8(4):777-95
pubmed: 27053445
Genes Dev. 2005 Oct 15;19(20):2424-34
pubmed: 16195414
Genetics. 1988 Jan;118(1):75-86
pubmed: 8608934