Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10

Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While...

Descripción completa

Detalles Bibliográficos
Autores: López-Ayllón, Blanca D., Marín Martínez, Silvia, Fariñas Fernández, Marco, García-García, Tránsito, Fernández-Rodríguez, Raúl, de Lucas-Rius, Ana, Redondo, Natalia, Mendoza-García, Laura, Foguet, Carles, Grigas, Juozas, Calvet, Alba, Villalba, José Manuel, Rodríguez Gómez, María Josefa, Megías, Diego, Mandracchia, Biagio, Luque, Daniel, Lozano Salvatella, Juan José, Calvo, Cristina, Merino Herrán, Unai, Thomson, Timothy M., Garrido, Juan J., Cascante i Serratosa, Marta, Montoya, María
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/218002
Acceso en línea:https://hdl.handle.net/2445/218002
Access Level:acceso abierto
Palabra clave:Metabolòmica
ADN mitocondrial
SARS-CoV-2
Metabolomics
Mitochondrial DNA
id ES_d79252bbaaedd9d0456109bbd36deb7e
oai_identifier_str oai:diposit.ub.edu:2445/218002
network_acronym_str ES
network_name_str España
repository_id_str
spelling Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10López-Ayllón, Blanca D.Marín Martínez, SilviaFariñas Fernández, MarcoGarcía-García, TránsitoFernández-Rodríguez, Raúlde Lucas-Rius, AnaRedondo, NataliaMendoza-García, LauraFoguet, CarlesGrigas, JuozasCalvet, AlbaVillalba, José ManuelRodríguez Gómez, María JosefaMegías, DiegoMandracchia, BiagioLuque, DanielLozano Salvatella, Juan JoséCalvo, CristinaMerino Herrán, UnaiThomson, Timothy M.Garrido, Juan J.Cascante i Serratosa, MartaMontoya, MaríaMetabolòmicaADN mitocondrialSARS-CoV-2MetabolomicsMitochondrial DNASARS-CoV-2Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.Wiley2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/218002Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1002/jmv.29752Journal of Medical Virology, 2024, vol. 96, num.7, p. 1-22https://doi.org/10.1002/jmv.29752cc-by-nc-nd (c) López-Ayllón, Blanca D. et al, 2024http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2180022026-05-27T06:46:51Z
dc.title.none.fl_str_mv Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10
title Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10
spellingShingle Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10
López-Ayllón, Blanca D.
Metabolòmica
ADN mitocondrial
SARS-CoV-2
Metabolomics
Mitochondrial DNA
SARS-CoV-2
title_short Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10
title_full Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10
title_fullStr Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10
title_full_unstemmed Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10
title_sort Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10
dc.creator.none.fl_str_mv López-Ayllón, Blanca D.
Marín Martínez, Silvia
Fariñas Fernández, Marco
García-García, Tránsito
Fernández-Rodríguez, Raúl
de Lucas-Rius, Ana
Redondo, Natalia
Mendoza-García, Laura
Foguet, Carles
Grigas, Juozas
Calvet, Alba
Villalba, José Manuel
Rodríguez Gómez, María Josefa
Megías, Diego
Mandracchia, Biagio
Luque, Daniel
Lozano Salvatella, Juan José
Calvo, Cristina
Merino Herrán, Unai
Thomson, Timothy M.
Garrido, Juan J.
Cascante i Serratosa, Marta
Montoya, María
author López-Ayllón, Blanca D.
author_facet López-Ayllón, Blanca D.
Marín Martínez, Silvia
Fariñas Fernández, Marco
García-García, Tránsito
Fernández-Rodríguez, Raúl
de Lucas-Rius, Ana
Redondo, Natalia
Mendoza-García, Laura
Foguet, Carles
Grigas, Juozas
Calvet, Alba
Villalba, José Manuel
Rodríguez Gómez, María Josefa
Megías, Diego
Mandracchia, Biagio
Luque, Daniel
Lozano Salvatella, Juan José
Calvo, Cristina
Merino Herrán, Unai
Thomson, Timothy M.
Garrido, Juan J.
Cascante i Serratosa, Marta
Montoya, María
author_role author
author2 Marín Martínez, Silvia
Fariñas Fernández, Marco
García-García, Tránsito
Fernández-Rodríguez, Raúl
de Lucas-Rius, Ana
Redondo, Natalia
Mendoza-García, Laura
Foguet, Carles
Grigas, Juozas
Calvet, Alba
Villalba, José Manuel
Rodríguez Gómez, María Josefa
Megías, Diego
Mandracchia, Biagio
Luque, Daniel
Lozano Salvatella, Juan José
Calvo, Cristina
Merino Herrán, Unai
Thomson, Timothy M.
Garrido, Juan J.
Cascante i Serratosa, Marta
Montoya, María
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Metabolòmica
ADN mitocondrial
SARS-CoV-2
Metabolomics
Mitochondrial DNA
SARS-CoV-2
topic Metabolòmica
ADN mitocondrial
SARS-CoV-2
Metabolomics
Mitochondrial DNA
SARS-CoV-2
description Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/218002
url https://hdl.handle.net/2445/218002
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1002/jmv.29752
Journal of Medical Virology, 2024, vol. 96, num.7, p. 1-22
https://doi.org/10.1002/jmv.29752
dc.rights.none.fl_str_mv cc-by-nc-nd (c) López-Ayllón, Blanca D. et al, 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) López-Ayllón, Blanca D. et al, 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869421016621514752
score 15,812429

Similares en LA Referencia