Mitochondrial immune response to SARS-CoV-2 (WP5038)

Homo sapiens

SARS-CoV-2 mitochondrial immune response


Gabriel Couillaud , Claire Billingsley , Egon Willighagen , Friederike Ehrhart , Eric Weitz , Finterly Hu , Kingson ''junsheng Thang'' Luc , and Nhung Pham


last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.


Homo sapiens




Pathway Ontology

immune response pathway disease pathway

Disease Ontology

COVID-19 severe acute respiratory syndrome


Label Type Compact URI Comment
cGAMP Metabolite chebi:71580
ROS Metabolite chebi:26523
angiotensin-(1-9) Metabolite chebi:80128
angiotensin II Metabolite chebi:2719 ang II accumulation
angiotensin I Metabolite chebi:2718
AGT Metabolite chebi:2720
angiotensin (1-7) Metabolite chebi:55438
AGTR2 GeneProduct ensembl:ENSG00000180772
MAS1 GeneProduct ensembl:ENSG00000206470
NOX1 GeneProduct uniprot:Q9Y5S8
AGTR1 GeneProduct ensembl:ENSG00000144891
cGAS GeneProduct uniprot:Q8N884
ACAD9 GeneProduct ensembl:ENSG00000177646
NFKB1 GeneProduct ensembl:ENSG00000109320
DDX58 GeneProduct ensembl:ENSG00000107201
IFIH1 GeneProduct hgnc.symbol:IFIH1
NDUFAF1 GeneProduct ensembl:ENSG00000137806
BCS1L GeneProduct ensembl:ENSG00000074582
ECSIT GeneProduct ensembl:ENSG00000130159
NDUFB9 GeneProduct ensembl:ENSG00000147684
IKBKE GeneProduct ensembl:ENSG00000263528
CTSL GeneProduct ensembl:ENSG00000135047
IRF3 GeneProduct ensembl:ENSG00000126456
NFKB2 GeneProduct ensembl:ENSG00000077150
TBK1 GeneProduct ensembl:ENSG00000183735
NLRX1 GeneProduct ensembl:ENSG00000160703
IRF3 GeneProduct ensembl:ENSG00000126456
TMPRSS2 GeneProduct ensembl:ENSG00000184012
ACE2 GeneProduct uniprot:Q9BYF1
IFN-I GeneProduct ncbigene:3438
TMEM173 GeneProduct uniprot:Q86WV6 STING1
TLR3 GeneProduct ensembl:ENSG00000164342
TICAM1 GeneProduct ncbigene:148022 TRIF
nsp13 GeneProduct wikidata:Q94648377
orf6 GeneProduct uniprot:P0DTC6
TRAF6 GeneProduct ensembl:ENSG00000175104
TRAF3 GeneProduct ensembl:ENSG00000131323
MAVS GeneProduct ensembl:ENSG00000088888
PHB GeneProduct uniprot:P35232
PHB2 GeneProduct uniprot:Q99623
TLR7 GeneProduct ensembl:ENSG00000196664
IRF7 GeneProduct ensembl:ENSG00000185507
S2 Protein wikidata:Q106020384 S2 subunit
S1 Protein wikidata:Q106020256 S1 subunit
HSP90 Protein ensembl:ENSG00000080824.19
orf9c Protein wikidata:Q104520877
nsp7 Protein uniprot:P0DTD1
ACE Protein uniprot:P12821
Renin Protein uniprot:A0A1B0GUZ2
Nucleoprotein N Protein uniprot:P0DTC9
Spike Glycoprotein S Protein uniprot:P0DTC2
Envelope Protein E Protein uniprot:P0DTC4
Membrane Glycoprotein M Protein uniprot:P0DTC5
nsp6 Protein ncbiprotein:YP_009725302
orf9b Protein uniprot:P0DTD2 promotes mitochondrial fusion
TOMM70 Protein ensembl:ENSG00000154174
nsp2 Protein uniprot:P0DTD1 impairs intra- cellular signaling and mitochondrial biogenesis
PLpro Protein uniprot:P0DTD2


  1. The insert sequence in SARS-CoV-2 enhances spike protein cleavage by TMPRSS [Internet]. Meng T, Cao H, Zhang H, Kang Z, Xu D, Gong H, et al. Cold Spring Harbor Laboratory; 2020. Available from: DOI Scholia
  2. SARS coronavirus and innate immunity. Frieman M, Heise M, Baric R. Virus Res. 2008 Apr;133(1):101–12. PubMed Europe PMC Scholia
  3. An N-terminal addressing sequence targets NLRX1 to the mitochondrial matrix. Arnoult D, Soares F, Tattoli I, Castanier C, Philpott DJ, Girardin SE. J Cell Sci. 2009 Sep 1;122(Pt 17):3161–8. PubMed Europe PMC Scholia
  4. Crosstalk of reactive oxygen species and NF-κB signaling. Morgan MJ, Liu Z gang. Cell Res. 2011 Jan;21(1):103–15. PubMed Europe PMC Scholia
  5. Mitochondria in innate immune responses. West AP, Shadel GS, Ghosh S. Nat Rev Immunol. 2011 Jun;11(6):389–402. PubMed Europe PMC Scholia
  6. NLRX1 protein attenuates inflammatory responses to infection by interfering with the RIG-I-MAVS and TRAF6-NF-κB signaling pathways. Allen IC, Moore CB, Schneider M, Lei Y, Davis BK, Scull MA, et al. Immunity. 2011 Jun 24;34(6):854–65. PubMed Europe PMC Scholia
  7. The NLR protein, NLRX1, and its partner, TUFM, reduce type I interferon, and enhance autophagy. Lei Y, Wen H, Ting JPY. Autophagy. 2013 Mar;9(3):432–3. PubMed Europe PMC Scholia
  8. NLRX1 Mediates MAVS Degradation To Attenuate the Hepatitis C Virus-Induced Innate Immune Response through PCBP2. Qin Y, Xue B, Liu C, Wang X, Tian R, Xie Q, et al. J Virol. 2017 Nov 14;91(23):e01264-17. PubMed Europe PMC Scholia
  9. Mitochondrial electron transport chain, ROS generation and uncoupling (Review). Zhao RZ, Jiang S, Zhang L, Yu ZB. Int J Mol Med. 2019 Jul;44(1):3–15. PubMed Europe PMC Scholia
  10. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. Nature. 2020 Jul;583(7816):459–68. PubMed Europe PMC Scholia
  11. The mechanistic overview of SARS-CoV-2 using angiotensin-converting enzyme 2 to enter the cell for replication: possible treatment options related to the renin-angiotensin system. Offringa A, Montijn R, Singh S, Paul M, Pinto YM, Pinto-Sietsma SJ. Eur Heart J Cardiovasc Pharmacother. 2020 Sep 1;6(5):317–25. PubMed Europe PMC Scholia
  12. Kawasaki-like diseases and thrombotic coagulopathy in COVID-19: delayed over-activation of the STING pathway? Berthelot JM, Drouet L, Lioté F. Emerg Microbes Infect. 2020 Dec;9(1):1514–22. PubMed Europe PMC Scholia
  13. Comparative multiplexed interactomics of SARS-CoV-2 and homologous coronavirus non-structural proteins identifies unique and shared host-cell dependencies. Davies JP, Almasy KM, McDonald EF, Plate L. bioRxiv. 2020 Jul 14;2020.07.13.201517. PubMed Europe PMC Scholia
  14. Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Shin D, Mukherjee R, Grewe D, Bojkova D, Baek K, Bhattacharya A, et al. Nature. 2020 Nov;587(7835):657–62. PubMed Europe PMC Scholia
  15. SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70. Jiang HW, Zhang HN, Meng QF, Xie J, Li Y, Chen H, et al. Cell Mol Immunol. 2020 Sep;17(9):998–1000. PubMed Europe PMC Scholia
  16. Genes encoding ACE2, TMPRSS2 and related proteins mediating SARS-CoV-2 viral entry are upregulated with age in human cardiomyocytes. Robinson EL, Alkass K, Bergmann O, Maguire JJ, Roderick HL, Davenport AP. J Mol Cell Cardiol. 2020 Oct;147:88–91. PubMed Europe PMC Scholia
  17. SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells. Dominguez Andres A, Feng Y, Campos AR, Yin J, Yang CC, James B, et al. bioRxiv. 2020 Aug 19;2020.08.18.256776. PubMed Europe PMC Scholia
  18. Evasion of Type I Interferon by SARS-CoV-2. Xia H, Cao Z, Xie X, Zhang X, Chen JYC, Wang H, et al. Cell Rep. 2020 Oct 6;33(1):108234. PubMed Europe PMC Scholia
  19. SARS-CoV-2 induces double-stranded RNA-mediated innate immune responses in respiratory epithelial derived cells and cardiomyocytes. Li Y, Renner DM, Comar CE, Whelan JN, Reyes HM, Cardenas-Diaz FL, et al. bioRxiv. 2020 Nov 2;2020.09.24.312553. PubMed Europe PMC Scholia
  20. Mitochondria: In the Cross Fire of SARS-CoV-2 and Immunity. Burtscher J, Cappellano G, Omori A, Koshiba T, Millet GP. iScience. 2020 Oct 23;23(10):101631. PubMed Europe PMC Scholia
  21. The Mitochondrial Outer Membrane Protein Tom70-Mediator in Protein Traffic, Membrane Contact Sites and Innate Immunity. Kreimendahl S, Rassow J. Int J Mol Sci. 2020 Oct 1;21(19):7262. PubMed Europe PMC Scholia
  22. Role of Oxidative Stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) Infection: A Review. Suhail S, Zajac J, Fossum C, Lowater H, McCracken C, Severson N, et al. Protein J. 2020 Dec;39(6):644–56. PubMed Europe PMC Scholia
  23. Coronavirus biology and replication: implications for SARS-CoV-2. V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Nat Rev Microbiol. 2021 Mar;19(3):155–70. PubMed Europe PMC Scholia
  24. Experimental and natural evidence of SARS-CoV-2-infection-induced activation of type I interferon responses. Banerjee A, El-Sayes N, Budylowski P, Jacob RA, Richard D, Maan H, et al. iScience. 2021 May 21;24(5):102477. PubMed Europe PMC Scholia