SARS-CoV-2 mitochondrial chronic oxidative stress and endothelial dysfunction (Homo sapiens)

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MitochondriumCellNucleusp90rskorf9cElectron Transport Chain (OXPHOS)TERF2IPIL-18TERF2NDUFAF2IL-1βMtROSnsp7SIRT6NF-kBIL-6NDUFAF1NLRP3TNF556, 8762, 652, 855555485SARS-CoV-23ACAD99ECSIT9BCS1KL9Mitochondrial CIII assembly6NLRX18Autophagy6Interleukin-1 Induced Activation of NF-kappa-B6MAVSTOMM701, 2TRAF31, 21, 2TRAF61, 2orf9b6NFIP2 2Oxidative Stress Induced Senescence 5DNA damage Telomere Shortening55RIG-I2PHB12nsp22, 6Glycolysis6PGC12Mitophagy6Angiotensin IAngiotensin II2, 6Angiotensin-(1-9)2, 6Angiotensin (1-7)2, 62, 6NOX1TMEM17322ACE22AGTACE22Renin2


Description

Long COVID-19 (Coronavirus disease) ranges from lingering symptoms 6-12 months after contracting COVID-19 to severe implications caused by the virus. To understand the (molecular) mechanisms underlying Long COVID-19 and the potential role of chronic oxidative stress, this pathway concisely visualises mitochondrial hijacking by SARS-COV-2 leading to pro-senescent mitochondrial dysfunction and inflammation.

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Bibliography

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  1. Gatti P, Ilamathi HS, Todkar K, Germain M; ''Mitochondria Targeted Viral Replication and Survival Strategies-Prospective on SARS-CoV-2.''; Front Pharmacol, 2020 PubMed Europe PMC Scholia
  2. Burtscher J, Cappellano G, Omori A, Koshiba T, Millet GP; ''Mitochondria: In the Cross Fire of SARS-CoV-2 and Immunity.''; iScience, 2020 PubMed Europe PMC Scholia
  3. Kumar V; ''Understanding the complexities of SARS-CoV2 infection and its immunology: A road to immune-based therapeutics.''; Int Immunopharmacol, 2020 PubMed Europe PMC Scholia
  4. Brendan Miller, Ana Silverstein, Melanie Flores, Kevin Cao, Hiroshi Kumagai, Hemal H Mehta, Kelvin Yen, Su- Jeong Kim, Pinchas Cohen; ''Host mitochondrial transcriptome response to SARS-CoV-2 in multiple cell models and clinical samples''; nature, 2021 PubMed Europe PMC Scholia
  5. Hemmat N, Asadzadeh Z, Ahangar NK, Alemohammad H, Najafzadeh B, Derakhshani A, Baghbanzadeh A, Baghi HB, Javadrashid D, Najafi S, Ar Gouilh M, Baradaran B; ''The roles of signaling pathways in SARS-CoV-2 infection; lessons learned from SARS-CoV and MERS-CoV.''; Arch Virol, 2021 PubMed Europe PMC Scholia
  6. Chang R, Mamun A, Dominic A, Le NT; ''SARS-CoV-2 Mediated Endothelial Dysfunction: The Potential Role of Chronic Oxidative Stress.''; Front Physiol, 2020 PubMed Europe PMC Scholia
  7. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu-Ozturk D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, García-Sastre A, Shokat KM, Shoichet BK, Krogan NJ.; ''A SARS-CoV-2 protein interaction map reveals targets for drug repurposing''; Nature , 2020 PubMed Europe PMC Scholia
  8. Kumar V; ''Understanding the complexities of SARS-CoV2 infection and its immunology: A road to immune-based therapeutics.''; Int Immunopharmacol, 2020 PubMed Europe PMC Scholia
  9. Sebastian Kreimendahl, Joachim Rassow; ''The Mitochondrial Outer Membrane Protein Tom70-Mediator in Protein Traffic, Membrane Contact Sites and Innate Immunity''; iscience, 2020 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
134567view22:51, 22 July 2024EweitzOntology Term : 'long COVID' added !
124655view13:26, 18 November 2022IsabelWassinkViral protein shape changed to rounded protein and viral protein names changed to lower case
122816view08:47, 21 May 2022EgonwCurated the PubMed identifiers.
122548view08:59, 15 April 2022KJTLUCModified description
122380view10:20, 26 March 2022EgonwRemoved a duplicate reference
122379view10:13, 26 March 2022EgonwModified description
122378view10:12, 26 March 2022EgonwModified title
122338view20:57, 20 March 2022KJTLUCAdded interactions to cytokines
122337view20:54, 20 March 2022KJTLUCFinal fixes: Removed Complex of cytokines, properly connected them Solved unconnected nodes
122284view13:58, 17 March 2022JingjingcaiWP5183.literature2
122270view10:51, 17 March 2022Jingjingcaiskillsclip
121853view19:18, 7 March 2022EgonwRemoved space in the PubMed identifier
121839view15:18, 7 March 2022JingjingcaiPathway Sars-CoV-2 with literature
121835view12:03, 7 March 2022CMalyarReference added for NDUFAF2
121822view22:44, 6 March 2022KJTLUCModified description
121820view22:42, 6 March 2022KJTLUCModified title
121819view22:41, 6 March 2022KJTLUCModified description
121818view22:34, 6 March 2022KJTLUCMoved "Cell" "Mitochondrium" Labels to the bottom and right for readability
121817view22:32, 6 March 2022KJTLUCCompacted Figure, enhanced readibility
121816view22:29, 6 March 2022KJTLUCConnected nodes and clarified interactions
121815view22:25, 6 March 2022KJTLUCUpdated References + Added extra elements; such as effects of Oxidative Stress induced senescence
121814view22:09, 6 March 2022KJTLUCUpdated References
121813view22:04, 6 March 2022KJTLUCUpdated References
121812view21:55, 6 March 2022KJTLUCAdded References
121811view21:53, 6 March 2022KJTLUCAdding References
121810view21:48, 6 March 2022KJTLUCUpdated Label for NSP2
121803view14:16, 6 March 2022EgonwReverted to version '15:12, 27 February 2022' by Egonw
121802view14:15, 6 March 2022EgonwReverted to version '14:21, 5 March 2022' by Egonw
121801view14:13, 6 March 2022EgonwNot a conversion
121799view14:21, 5 March 2022Jingjingcaiinitial SARS-CoV-2 infection via Endothelial ACE2
121732view15:12, 27 February 2022CMalyarAdded NFIP2/ PBHB1 / NSP2 (Missing identifier to be solved soon)
121731view14:18, 27 February 2022KJTLUCCell Size adjusted
121589view17:44, 21 February 2022KJTLUCAdded green links
121576view14:29, 21 February 2022Mkutmonfix Ensembl annotation
121575view14:28, 21 February 2022MkutmonOntology Term : 'oxidative stress response pathway' added !
121574view14:28, 21 February 2022MkutmonOntology Term : 'signaling pathway' added !
121573view14:27, 21 February 2022MkutmonOntology Term : 'COVID-19' added !
121559view11:29, 21 February 2022KJTLUCAdded Celine's contribution
121558view11:25, 21 February 2022KJTLUCArrow fixed
121525view23:33, 20 February 2022KJTLUCCompacted
121524view23:31, 20 February 2022KJTLUCUpdated Pathways and enhanced clearity
121523view23:12, 20 February 2022KJTLUCUpdated Pathways
121522view23:00, 20 February 2022KJTLUCUpdated Pathways and Added additional data
121520view22:22, 20 February 2022KJTLUCMinor Changes to Layout
121519view22:17, 20 February 2022KJTLUCMinor Changes to font and enhanced readability
121518view22:11, 20 February 2022KJTLUCUpdated annotations and protein databases
121517view21:52, 20 February 2022KJTLUCUpdated Font and Sizes to enhance readability
121236view23:27, 13 February 2022KJTLUCUpdated description Cell
121235view23:26, 13 February 2022KJTLUCAdded SARS-COV-2 Virus on outside of cell
121234view23:23, 13 February 2022KJTLUCNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ACAD9GeneProductENSG00000177646 (Ensembl)
ACE2GeneProductQ9BYF1 (Uniprot-TrEMBL)
ACEGeneProductP12821 (Uniprot-TrEMBL)
AGTGeneProductP01019 (Uniprot-TrEMBL)
Angiotensin (1-7) Metabolite55438 (ChEBI)
Angiotensin I Metabolite2718 (ChEBI)
Angiotensin II Metabolite2719 (ChEBI)
Angiotensin-(1-9) Metabolite80128 (ChEBI)
AutophagyPathwayWP4936 (WikiPathways)
BCS1KLGeneProductENSG00000074582 (Ensembl)
DNA damage PathwayWP707 (WikiPathways)
ECSITGeneProductENSG00000130159 (Ensembl)
Electron Transport Chain (OXPHOS) PathwayWP111 (WikiPathways)
Glycolysis PathwayWP5049 (WikiPathways)
IL-18 ProteinQ14116 (Uniprot-TrEMBL)
IL-1βProteinCHEBI:138181 (ChEBI)
IL-6 ProteinP05231 (Uniprot-TrEMBL)
Interleukin-1 Induced Activation of NF-kappa-BPathwayWP3656 (WikiPathways)
MAVSGeneProductENSG00000088888 (Ensembl)
Mitochondrial CIII assembly PathwayWP4921 (WikiPathways)
MitophagyPathwayWP3549 (WikiPathways)
MtROS Metabolite26523 (ChEBI)
NDUFAF1GeneProductENSG00000137806 (Ensembl)
NDUFAF2GeneProductENSG00000164182 (Ensembl)
NF-kBGeneProductENSG00000109320 (Ensembl)
NFIP2 GeneProductQ9NV92 (Uniprot-TrEMBL)
NLRP3GeneProductENSG00000162711 (Ensembl)
NLRX1GeneProductENSG00000160703 (Ensembl)
NOX1GeneProductQ9Y5S8 (Uniprot-TrEMBL)
Oxidative Stress Induced Senescence PathwayWP3404 (WikiPathways)
PGC1MetaboliteCHEBI:15546 (ChEBI)
PHB1GeneProductP35232 (Uniprot-TrEMBL)
RIG-IGeneProduct095786 (Uniprot-TrEMBL)
ReninGeneProductP00797 (Uniprot-TrEMBL)
SIRT6GeneProductENSG00000077463 (Ensembl)
TERF2GeneProductENSG00000132604 (Ensembl)
TERF2IPGeneProductENSG00000166848 (Ensembl)
TMEM173GeneProductQ86WV6 (Uniprot-TrEMBL)
TNFProteinQ5STB3 (Uniprot-TrEMBL)
TOMM70GeneProductENSG00000154174 (Ensembl)
TRAF3GeneProductENSG00000131323 (Ensembl)
TRAF6GeneProductENSG00000175104 (Ensembl)
Telomere ShorteningPathwayWP3565 (WikiPathways)
nsp2ProteinYP_009725298 (NCBI Protein)
nsp7ProteinP0DTD1 (Uniprot-TrEMBL)
orf9bProteinP0DTD2 (Uniprot-TrEMBL)
orf9cProteinP0DTD3 (Uniprot-TrEMBL)
p90rskProteinE9PGT3 (Uniprot-TrEMBL)

Annotated Interactions

No annotated interactions

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