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SARS-CoV-2 mitochondrial metabolic and epigenomic reprogramming in COVID-19.
Guarnieri, Joseph W; Haltom, Jeffrey A; Albrecht, Yentli E Soto; Lie, Timothy; Olali, Arnold Z; Widjaja, Gabrielle A; Ranshing, Sujata S; Angelin, Alessia; Murdock, Deborah; Wallace, Douglas C.
Afiliação
  • Guarnieri JW; Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Haltom JA; Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Albrecht YES; Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Lie T; Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Olali AZ; Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Widjaja GA; Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Ranshing SS; Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Angelin A; Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Murdock D; Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Wallace DC; Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Division of Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: WallaceD1@chop.edu.
Pharmacol Res ; 204: 107170, 2024 Jun.
Article em En | MEDLINE | ID: mdl-38614374
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosforilação Oxidativa / SARS-CoV-2 / COVID-19 / Mitocôndrias Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosforilação Oxidativa / SARS-CoV-2 / COVID-19 / Mitocôndrias Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article