The Orf9b protein of SARS-CoV-2 modulates mitochondrial protein biogenesis.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
02 10 2023
02 10 2023
Historique:
received:
01
03
2023
revised:
06
07
2023
accepted:
07
08
2023
pmc-release:
08
03
2024
medline:
11
9
2023
pubmed:
8
9
2023
entrez:
8
9
2023
Statut:
ppublish
Résumé
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) expresses high amounts of the protein Orf9b to target the mitochondrial outer membrane protein Tom70. Tom70 serves as an import receptor for mitochondrial precursors and, independently of this function, is critical for the cellular antiviral response. Previous studies suggested that Orf9b interferes with Tom70-mediated antiviral signaling, but its implication for mitochondrial biogenesis is unknown. In this study, we expressed Orf9b in human HEK293 cells and observed an Orf9b-mediated depletion of mitochondrial proteins, particularly in respiring cells. To exclude that the observed depletion was caused by the antiviral response, we generated a yeast system in which the function of human Tom70 could be recapitulated. Upon expression of Orf9b in these cells, we again observed a specific decline of a subset of mitochondrial proteins and a general reduction of mitochondrial volume. Thus, the SARS-CoV-2 virus is able to modulate the mitochondrial proteome by a direct effect of Orf9b on mitochondrial Tom70-dependent protein import.
Identifiants
pubmed: 37682539
pii: 276244
doi: 10.1083/jcb.202303002
pmc: PMC10491932
pii:
doi:
Substances chimiques
Coronavirus Nucleocapsid Proteins
0
Membrane Proteins
0
Mitochondrial Membrane Transport Proteins
0
nucleocapsid phosphoprotein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : European Research Council
ID : 101052639
Pays : International
Informations de copyright
© 2023 Lenhard et al.
Références
Science. 2018 Apr 13;360(6385):
pubmed: 29650645
Bioinformatics. 2004 Nov 1;20(16):2778-86
pubmed: 15166021
Antioxid Redox Signal. 2023 Mar;38(7-9):599-618
pubmed: 36053670
Nature. 2021 Jun;594(7862):246-252
pubmed: 33845483
Nat Protoc. 2016 Dec;11(12):2301-2319
pubmed: 27809316
Cell. 2005 Sep 9;122(5):645-7
pubmed: 16143094
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Sep 1;66(Pt 9):985-9
pubmed: 20823510
J Cell Sci. 2002 May 1;115(Pt 9):1895-905
pubmed: 11956321
Nature. 2022 Oct;610(7931):381-388
pubmed: 36198800
Elife. 2022 Mar 02;11:
pubmed: 35234609
Microb Pathog. 2022 Sep;170:105699
pubmed: 35944840
Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12536-41
pubmed: 10535957
Nature. 2022 Feb;602(7897):487-495
pubmed: 34942634
J Mol Biol. 2006 May 12;358(4):1010-22
pubmed: 16566938
Nature. 2019 May;569(7758):679-683
pubmed: 31118508
Biol Cell. 2021 Jul;113(7):311-328
pubmed: 33666950
Int J Mol Sci. 2021 Aug 26;22(17):
pubmed: 34502139
J Cell Biol. 1993 Nov;123(4):785-98
pubmed: 8227140
Mol Biol Cell. 2012 Oct;23(20):3957-69
pubmed: 22918950
Nat Commun. 2021 May 14;12(1):2843
pubmed: 33990585
Commun Biol. 2022 Jan 12;5(1):45
pubmed: 35022513
Redox Biol. 2021 Jul;43:101976
pubmed: 33932869
Nucleic Acids Res. 2021 Jan 8;49(D1):D1541-D1547
pubmed: 33174596
Science. 2018 Sep 14;361(6407):1118-1122
pubmed: 30213914
Int J Mol Sci. 2020 Oct 01;21(19):
pubmed: 33019591
Cell Metab. 2021 Dec 7;33(12):2464-2483.e18
pubmed: 34800366
J Biol Chem. 2016 Sep 2;291(36):18620-31
pubmed: 27402847
Cell Rep. 2017 Jun 27;19(13):2836-2852
pubmed: 28658629
J Virol. 2010 Jul;84(13):6400-9
pubmed: 20410282
J Immunol. 2014 Sep 15;193(6):3080-9
pubmed: 25135833
Trends Cell Biol. 2014 Dec;24(12):761-70
pubmed: 25189346
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Nat Methods. 2014 Mar;11(3):319-24
pubmed: 24487582
J Biol Chem. 1994 Apr 22;269(16):11893-901
pubmed: 8163488
Nucleic Acids Res. 1992 Mar 25;20(6):1425
pubmed: 1561104
Curr Biol. 2018 Feb 5;28(3):369-382.e6
pubmed: 29395920
Nature. 1996 Dec 5;384(6608):432-8
pubmed: 8945469
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
Aging Cell. 2022 Nov;21(11):e13727
pubmed: 36219531
Cell Mol Immunol. 2020 Sep;17(9):998-1000
pubmed: 32728199
J Cell Biol. 2021 Nov 1;220(11):
pubmed: 34694322
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Nat Rev Immunol. 2022 Jan;22(1):47-56
pubmed: 34837062
J Cell Physiol. 2022 Jul;237(7):2913-2928
pubmed: 35460571
Med Sci Monit. 2015 Jun 16;21:1745-51
pubmed: 26079849
J Proteome Res. 2011 Apr 1;10(4):1794-805
pubmed: 21254760
Annu Rev Cell Dev Biol. 2020 Oct 6;36:265-289
pubmed: 33021820
Cell Res. 2010 Sep;20(9):994-1011
pubmed: 20628368
J Clin Med. 2019 Jul 21;8(7):
pubmed: 31330880
EMBO Mol Med. 2020 Dec 7;12(12):e13001
pubmed: 33078545
Bio Protoc. 2021 Jun 20;11(12):e4057
pubmed: 34263000
Proc Natl Acad Sci U S A. 2021 Jun 22;118(25):
pubmed: 34083352
Nature. 2021 Jan;589(7840):125-130
pubmed: 32906143
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450
pubmed: 30395289
EMBO J. 1993 Nov;12(11):4115-23
pubmed: 8223428
Cell Rep. 2018 Nov 20;25(8):2036-2043.e5
pubmed: 30463002
Science. 2022 Jan 14;375(6577):eabi4343
pubmed: 35025629
Biol Chem. 2019 Aug 27;400(9):1229-1240
pubmed: 31199753
Bio Protoc. 2018 Sep 05;8(17):e2474
pubmed: 34395785
Biol Chem. 2021 Jul 05;402(8):937-943
pubmed: 34218542
EMBO J. 1983;2(12):2169-72
pubmed: 6365533
Cell Rep. 2021 Apr 6;35(1):108936
pubmed: 33826901
Nat Struct Mol Biol. 2006 Jul;13(7):589-93
pubmed: 16767096
J Cell Biol. 2017 Sep 4;216(9):2679-2689
pubmed: 28774891
Mol Cell Biochem. 2023 Jun;478(6):1325-1343
pubmed: 36308668
Science. 2022 Oct 21;378(6617):317-322
pubmed: 36264797
J Mol Biol. 2013 Dec 13;425(24):5009-19
pubmed: 24120683
J Microsc. 2006 Dec;224(Pt 3):213-32
pubmed: 17210054
Genetics. 1989 May;122(1):19-27
pubmed: 2659436
Genome Biol. 2016 Mar 08;17:45
pubmed: 26956608
J Biol Chem. 1993 Jan 5;268(1):449-54
pubmed: 8380165
Nat Protoc. 2013 Nov;8(11):2281-2308
pubmed: 24157548
Cell Rep. 2015 Jul 7;12(1):7-14
pubmed: 26119743
J Cell Biol. 1990 Dec;111(6 Pt 1):2353-63
pubmed: 2177474
EMBO Rep. 2008 Jan;9(1):63-9
pubmed: 18007655
J Cell Biol. 2015 May 25;209(4):539-48
pubmed: 25987606
Nature. 2020 Jul;583(7816):469-472
pubmed: 32408336
Cell. 2003 Jan 10;112(1):41-50
pubmed: 12526792
Bioinformatics. 2007 May 1;23(9):1164-7
pubmed: 17344241
Nat Commun. 2015 Jul 17;6:7811
pubmed: 26183716
EMBO J. 1997 Jul 16;16(14):4267-75
pubmed: 9250670
Cell Rep. 2021 Feb 16;34(7):108761
pubmed: 33567255
J Biol Chem. 2009 Aug 28;284(35):23852-9
pubmed: 19581297
Sci Rep. 2019 Feb 19;9(1):2234
pubmed: 30783202
J Cell Biol. 2018 Apr 2;217(4):1369-1382
pubmed: 29382700
J Biol Chem. 2009 Nov 13;284(46):31635-46
pubmed: 19767391
Nucleic Acids Res. 2004 Mar 19;32(5):1792-7
pubmed: 15034147