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Título: | Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 |
Autor: | López-Ayllón, Blanca D. CSIC ORCID; Marin, Silvia; Farinas Fernández, Marcos; García-García, Tránsito; Fernández-Rodríguez, Raúl; Lucas-Rius, Ana de CSIC; Redondo, Natalia CSIC ORCID ; Mendoza-García, Laura CSIC; Foguet, Carles; Grigas, Juozas; Calvet, Alba; Villalba, José Manuel; Rodríguez Gómez, María Josefa; Megías, Diego; Mandracchia, Biagio; Lozano, Juan José; Calvo, Cristina CSIC; Thomson, Timothy M. CSIC ORCID ; Garrido, Juan J.; Cascante, Marta CSIC ORCID; Montoya, María CSIC ORCID | Palabras clave: | ORF3a ORF9b ORF9c ORF10 Mitochondria Transcriptomics Metabolomics Genome-scale metabolic modeling (GSMM) |
Fecha de publicación: | 26-sep-2023 | Editor: | BioRxiv | Citación: | López-Ayllón, Blanca D.; Marin, Silvia; Farinas Fernández, Marcos; Fernández-Rodríguez, Raúl; Lucas-Rius, Ana de; 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, Juan José; Calvo, Cristina; Thomson, Timothy M.; Garrido, Juan J.; Cascante, Marta; Montoya, María; 2023; Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10; BioRxiv; https://doi.org/10.1101/2023.09.26.559506 | Resumen: | Antiviral signaling, immune response and cell metabolism in human body are dysregulated by SARS-CoV-2, the causative agent of the 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 all four ORFs caused mitochondrial fragmentation and altered mitochondrial function, only ORF3a and ORF9c induced a marked structural alteration in mitochondrial cristae. ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes. In contrast, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes for proteins with critical mitochondrial functions and morphology. Genome-Scale Metabolic Models predicted common and private metabolic flux reprogramming, notably a depressed amino acid metabolism, and an enhanced metabolism of specific lipids 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. | Versión del editor: | https://doi.org/10.1101/2023.09.26.559506 | URI: | http://hdl.handle.net/10261/335867 | DOI: | https://doi.org/10.20350/digitalCSIC/15585 |
Aparece en las colecciones: | (PTI Salud Global) Colección Especial COVID-19 (CIB) Artículos (IBMB) Artículos |
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