Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response.
Cell Death
Inflammation
Mitochondria
NF-κB
Ubiquitin
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
received:
20
02
2023
accepted:
16
01
2024
revised:
15
01
2024
medline:
18
3
2024
pubmed:
10
2
2024
entrez:
10
2
2024
Statut:
ppublish
Résumé
Mitochondrial outer membrane permeabilisation (MOMP) is often essential for apoptosis, by enabling cytochrome c release that leads to caspase activation and rapid cell death. Recently, MOMP has been shown to be inherently pro-inflammatory with emerging cellular roles, including its ability to elicit anti-tumour immunity. Nonetheless, how MOMP triggers inflammation and how the cell regulates this remains poorly defined. We find that upon MOMP, many proteins localised either to inner or outer mitochondrial membranes are ubiquitylated in a promiscuous manner. This extensive ubiquitylation serves to recruit the essential adaptor molecule NEMO, leading to the activation of pro-inflammatory NF-κB signalling. We show that disruption of mitochondrial outer membrane integrity through different means leads to the engagement of a similar pro-inflammatory signalling platform. Therefore, mitochondrial integrity directly controls inflammation, such that permeabilised mitochondria initiate NF-κB signalling.
Identifiants
pubmed: 38337057
doi: 10.1038/s44318-024-00044-1
pii: 10.1038/s44318-024-00044-1
pmc: PMC10943237
doi:
Substances chimiques
NF-kappa B
0
Ubiquitin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
904-930Subventions
Organisme : Cancer Research UK
ID : 29256
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 29800
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 27603
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 27323
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S00811X/1
Pays : United Kingdom
Informations de copyright
© 2024. The Author(s).
Références
Cell Death Differ. 2018 Mar;25(4):784-796
pubmed: 29229994
Annu Rev Biochem. 2012;81:203-29
pubmed: 22524316
EMBO J. 2019 Jun 3;38(11):
pubmed: 30979778
Mol Cell. 2019 Apr 4;74(1):19-31.e7
pubmed: 30878284
Nature. 2013 Apr 18;496(7445):372-6
pubmed: 23503661
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552
pubmed: 34723319
Cell Death Differ. 2020 Aug;27(8):2297-2312
pubmed: 32015503
Elife. 2019 Feb 04;8:
pubmed: 30714902
Trends Immunol. 2022 Feb;43(2):148-162
pubmed: 35033428
EMBO Rep. 2009 Jul;10(7):748-54
pubmed: 19407830
EMBO J. 2018 Sep 3;37(17):
pubmed: 30049712
Cell Death Differ. 2014 Dec;21(12):1862-76
pubmed: 25080938
J Cell Biol. 2005 May 9;169(3):425-34
pubmed: 15866887
Science. 2018 Feb 23;359(6378):
pubmed: 29472455
Cell Rep. 2016 Mar 29;14(12):2846-58
pubmed: 26997266
Nat Rev Immunol. 2023 Mar;23(3):159-173
pubmed: 35879417
Nature. 2004 Dec 23;432(7020):1032-6
pubmed: 15525940
Nat Biotechnol. 2010 Aug;28(8):868-73
pubmed: 20639865
Nucleic Acids Res. 2021 Jan 8;49(D1):D1541-D1547
pubmed: 33174596
Nat Cell Biol. 2017 Sep;19(9):1116-1129
pubmed: 28846096
Cold Spring Harb Perspect Biol. 2013 Apr 01;5(4):a008656
pubmed: 23545416
Mol Cell. 2015 Mar 5;57(5):860-872
pubmed: 25702873
Cell. 2007 Jun 1;129(5):983-97
pubmed: 17540177
Mol Cell. 2020 Mar 5;77(5):1107-1123.e10
pubmed: 32142684
EMBO J. 2022 Dec 15;41(24):e112006
pubmed: 36398858
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Nature. 2009 Apr 9;458(7239):732-6
pubmed: 19360080
Mol Cell. 2023 Sep 7;83(17):3188-3204.e7
pubmed: 37683611
Nat Microbiol. 2017 May 08;2:17063
pubmed: 28481331
J Proteome Res. 2011 Apr 1;10(4):1794-805
pubmed: 21254760
J Biol Chem. 2009 Jan 30;284(5):2902-2907
pubmed: 19033441
Cell Death Dis. 2019 Jul 19;10(8):556
pubmed: 31324752
EMBO J. 2009 Oct 7;28(19):2885-95
pubmed: 19763089
Cell. 2009 Mar 20;136(6):1098-109
pubmed: 19303852
Nat Immunol. 2020 May;21(5):546-554
pubmed: 32231300
Nat Rev Mol Cell Biol. 2023 Mar;24(3):167-185
pubmed: 36302887
Cell Rep. 2015 Dec 1;13(9):2027-36
pubmed: 26655912
Nat Rev Mol Cell Biol. 2020 Feb;21(2):85-100
pubmed: 31636403
Mol Biol Cell. 2009 Dec;20(23):4871-84
pubmed: 19793916
Cell Rep. 2017 Sep 19;20(12):2846-2859
pubmed: 28930681
Nat Med. 2018 Feb;24(2):186-193
pubmed: 29334375
Int J Mol Sci. 2020 May 27;21(11):
pubmed: 32471110
Nat Microbiol. 2017 May 08;2:17066
pubmed: 28481361
Cell Death Differ. 2023 Feb;30(2):304-312
pubmed: 36447047
Nucleic Acids Res. 2020 Jan 8;48(D1):D1145-D1152
pubmed: 31686107
Immunity. 2011 Oct 28;35(4):445-55
pubmed: 22035837
Cell Rep. 2014 Oct 9;9(1):153-165
pubmed: 25284787
Nat Methods. 2016 Sep;13(9):731-40
pubmed: 27348712
Dev Cell. 2022 May 23;57(10):1211-1225.e6
pubmed: 35447090
Nature. 2023 Oct;622(7983):627-636
pubmed: 37821702
Bioinformatics. 2017 Aug 01;33(15):2424-2426
pubmed: 28369169