SARS-CoV-2 ORF3c impairs mitochondrial respiratory metabolism, oxidative stress, and autophagic flux
Articolo
Data di Pubblicazione:
2023
Citazione:
SARS-CoV-2 ORF3c impairs mitochondrial respiratory metabolism, oxidative stress, and autophagic flux / A. Mozzi, M. Oldani, M.E. Forcella, C. Vantaggiato, G. Cappelletti, C. Pontremoli, F. Valenti, D. Forni, M. Saresella, M. Biasin, M. Sironi, P. Fusi, R. Cagliani. - In: ISCIENCE. - ISSN 2589-0042. - 26:7(2023 Jun 14), pp. 107118.1-107118.17. [10.1016/j.isci.2023.107118]
Abstract:
Coronaviruses encode a variable number of accessory proteins that are involved in host-virus interaction, suppression of immune responses, or immune evasion. SARS-CoV-2 encodes at least twelve accessory proteins, whose roles during infection have been studied. Nevertheless, the role of the ORF3c accessory protein, an alternative open reading frame of ORF3a, has remained elusive. Herein, we show that the ORF3c protein has a mitochondrial localization and alters mitochondrial metabolism, inducing a shift from glucose to fatty acids oxidation and enhanced oxidative phosphorylation. These effects result in increased ROS production and block of the autophagic flux. In particular, ORF3c affects lysosomal acidification, blocking the normal autophagic degradation process and leading to autolysosome accumulation. We also observed different effect on autophagy for SARS-CoV-2 and batCoV RaTG13 ORF3c proteins; the 36R and 40K sites are necessary and sufficient to determine these effects.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
ORF3c; SARS-CoV-2; accessory protein; autophagy; mitochondrial respiratory metabolism; oxidative stress
Elenco autori:
A. Mozzi, M. Oldani, M.E. Forcella, C. Vantaggiato, G. Cappelletti, C. Pontremoli, F. Valenti, D. Forni, M. Saresella, M. Biasin, M. Sironi, P. Fusi, R. Cagliani
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