Review SARS-CoV-2 Mitochondrial Metabolic and Epigenomic Reprogramming in COVID-19, 2024, Guarnieri et al.

SARS-CoV-2 Mitochondrial Metabolic and Epigenomic Reprogramming in COVID-19
Guarnieri; Haltom; Albrecht; Lie; Olali; Widjaja; Ranshing; Angelin; Murdock; Wallace

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-CoV2 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.

Link | PDF (Pharmacological Research) [Open Access]

 

A comprehensive review.

 

Sections / subtitles —

SARS-CoV-2 reprograms host cell metabolism to enhance viral replication

• SARS-CoV-2 viral proteins manipulate mitochondrial physiology
• SARS-CoV-2 inhibits OXPHOS, increases mROS, stabilizes HIF-1α, and induces glycolysis
• Mitochondrial ROS, HIF-1α, and glycolysis induction
• SARS-CoV-2 induces de novo nucleic purine and pyrimidine synthesis
• SARS-CoV-2 requires de novo fatty acid synthesis
• SARS-CoV-2 infection alters levels of NAD+/NADP+
• SARS-CoV-2 requires glutaminolysis
• Inhibition of OXPHOS causes activation of innate immunity and the ISR

SARS-CoV-2 inhibition of mitochondrial biogenesis: Contribution to mortality and long-COVID

• SARS-CoV-2 impacts nuclear and mitochondrial transcription
• SARS-CoV-2 regulates OXPHOS transcription via Orf8, Orf10, and metabolic modulation of the epigenome

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