2024/04/11 by Joseph W. Guarnieri, Jeffrey Haltom, Yentli E. Soto Albrecht +7 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · #Autophagy in Disease and Therapy #Long-Term Effects of COVID-19 #Mitochondrial Function and Pathology
paper · doi:10.1016/j.phrs.2024.107170
openalex publication_date 2024/04/11 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
To determine the effects of SARS-CoV-2 infection on cellular metabolism, we conducted an exhaustive survey of the cellular metabolic pathways modulated by SARS-CoV-2 infection and confirmed their importance for SARS-CoV-2 propagation by cataloging the effects of specific pathway inhibitors. This revealed that SARS-CoV-2 strongly inhibits mitochondrial oxidative phosphorylation (OXPHOS) resulting in increased mitochondrial reactive oxygen species (mROS) production. The elevated mROS stabilizes HIF-1α which redirects carbon molecules from mitochondrial oxidation through glycolysis and the pentose phosphate pathway (PPP) to provide substrates for viral biogenesis. mROS also induces the release of mitochondrial DNA (mtDNA) which activates innate immunity. The restructuring of cellular energy metabolism is mediated in part by SARS-CoV-2 Orf8 and Orf10 whose expression restructures nuclear DNA (nDNA) and mtDNA OXPHOS gene expression. These viral proteins likely alter the epigenome, either by directly altering histone modifications or by modulating mitochondrial metabolite substrates of epigenome modification enzymes, potentially silencing OXPHOS gene expression and contributing to long-COVID.