2026-04-18T02:12:07Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2180022025-12-04T21:11:29Zcom_2072_1057col_2072_478781col_2072_478917

00925njm 22002777a 4500 dc López-Ayllón, Blanca D. author Marín Martínez, Silvia author Fariñas Fernández, Marco author García-García, Tránsito author Fernández-Rodríguez, Raúl author de Lucas-Rius, Ana author Redondo, Natalia author Mendoza-García, Laura author Foguet, Carles author Grigas, Juozas author Calvet, Alba author Villalba, José Manuel author Rodríguez Gómez, María Josefa author Megías, Diego author Mandracchia, Biagio author Luque, Daniel author Lozano Salvatella, Juan José author Calvo, Cristina author Merino Herrán, Unai author Thomson, Timothy M. author Garrido, Juan J. author Cascante i Serratosa, Marta author Montoya, María author 2025-01-27T14:05:01Z 2025-01-27T14:05:01Z 2024-07-01 2025-01-27T14:05:01Z 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. Metabolòmica ADN mitocondrial SARS-CoV-2 Metabolomics Mitochondrial DNA SARS-CoV-2 Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10