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2024-07-01

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cc-by-nc-nd (c) López-Ayllón, Blanca D. et al, 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/218002

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

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https://doi.org/10.1002/jmv.29752

Resum

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.

Matèries

Metabolòmica, ADN mitocondrial, SARS-CoV-2

Matèries (anglès)

Metabolomics, Mitochondrial DNA, SARS-CoV-2

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Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

Citació

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. Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10. _Journal of Medical Virology_. 2024. Vol. 96, núm. 7, pàgs. 1-22. [consulta: 30 de gener de 2026]. ISSN: 0146-6615. [Disponible a: https://hdl.handle.net/2445/218002]

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