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...
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| Format: | Article |
| Publication date: | 2024 |
| Country: | España |
| Institution: | Instituto de Salud Carlos III (ISCIII) |
| Repository: | Repisalud |
| Language: | English |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/25445 |
| Online Access: | https://hdl.handle.net/20.500.12105/25445 |
| Access Level: | Open access |
| Keyword: | ORF10 ORF3a ORF9b ORF9c Genome‐scale metabolic modeling Metabolomics Mitochondria Transcriptomics A549 Cells COVID-19 Humans Open Reading Frames SARS-CoV-2 Transcriptome Viral Proteins Viral Regulatory and Accessory Proteins Viroporin Proteins |
| _version_ | 1878734466954821632 |
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| author | López-Ayllón, Blanca D |
| author2 | Marin, 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, María Josefa Megías, Diego Mandracchia, Biagio Luque, Daniel Lozano, Juan José Calvo, Cristina Merino Herrán, Unai Thomson, Timothy M Garrido, Juan J Cascante, Marta Montoya, Maria 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 author |
| author_browse | Calvet, Alba Calvo, Cristina Cascante, Marta Fariñas Fernández, Marco Fernández-Rodríguez, Raúl Foguet, Carles García-García, Tránsito Garrido, Juan J Grigas, Juozas Lozano, Juan José Luque, Daniel López-Ayllón, Blanca D Mandracchia, Biagio Marin, Silvia Megías, Diego Mendoza-García, Laura Merino Herrán, Unai Montoya, Maria Montoya, María Redondo, Natalia Rodríguez, María Josefa Thomson, Timothy M Villalba, José Manuel de Lucas-Rius, Ana |
| author_facet | López-Ayllón, Blanca D Marin, 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, María Josefa Megías, Diego Mandracchia, Biagio Luque, Daniel Lozano, Juan José Calvo, Cristina Merino Herrán, Unai Thomson, Timothy M Garrido, Juan J Cascante, Marta Montoya, Maria Montoya, María |
| author_role | author |
| collection | Repisalud |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_6a80e42e7f5fa4d5fdd0fa8588b9dbec |
| institution | Instituto de Salud Carlos III (ISCIII) |
| instname_str | Instituto de Salud Carlos III (ISCIII) |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:repisalud.isciii.es:20.500.12105/25445 |
| publishDate | 2024 |
| publishDateSort | 2024 |
| publisher | Wiley |
| publisherStr | Wiley |
| reponame_str | Repisalud |
| spelling | Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 López-Ayllón, Blanca D Marin, 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, María Josefa Megías, Diego Mandracchia, Biagio Luque, Daniel Lozano, Juan José Calvo, Cristina Merino Herrán, Unai Thomson, Timothy M Garrido, Juan J Cascante, Marta Montoya, Maria Montoya, María ORF10 ORF3a ORF9b ORF9c Genome‐scale metabolic modeling Metabolomics Mitochondria Transcriptomics A549 Cells COVID-19 Humans Open Reading Frames SARS-CoV-2 Transcriptome Viral Proteins Viral Regulatory and Accessory Proteins Viroporin Proteins 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. Wiley https://hdl.handle.net/20.500.12105/25445 |
| spellingShingle | Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 López-Ayllón, Blanca D ORF10 ORF3a ORF9b ORF9c Genome‐scale metabolic modeling Metabolomics Mitochondria Transcriptomics A549 Cells COVID-19 Humans Open Reading Frames SARS-CoV-2 Transcriptome Viral Proteins Viral Regulatory and Accessory Proteins Viroporin Proteins |
| title | 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_short | 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 |
| topic | ORF10 ORF3a ORF9b ORF9c Genome‐scale metabolic modeling Metabolomics Mitochondria Transcriptomics A549 Cells COVID-19 Humans Open Reading Frames SARS-CoV-2 Transcriptome Viral Proteins Viral Regulatory and Accessory Proteins Viroporin Proteins |
| topic_facet | ORF10 ORF3a ORF9b ORF9c Genome‐scale metabolic modeling Metabolomics Mitochondria Transcriptomics A549 Cells COVID-19 Humans Open Reading Frames SARS-CoV-2 Transcriptome Viral Proteins Viral Regulatory and Accessory Proteins Viroporin Proteins |
| url | https://hdl.handle.net/20.500.12105/25445 |