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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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SARS-CoV-2 ORF7a drives mitochondrial dysfunction via PDK4 activation and complex I inhibition

Raúl Fernández-Rodríguez1, Carmen M Soto-Jiménez1, Rebeca Acín-Pérez2

  • 1Department of Genetics, Immunogenomics and Molecular Pathogenesis Group, UIC Zoonoses and Emergent Diseases ENZOEM, University of Córdoba (UCO), Córdoba, Spain; Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain.

Cell Reports
|July 28, 2026
PubMed

Insights

The SARS-CoV-2 accessory protein ORF7a disrupts host cell metabolism. It impairs mitochondrial function by affecting glucose and lipid pathways, highlighting a new target for therapeutic intervention.

Area of Science:

  • Cell Biology
  • Virology
  • Metabolic Research

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters host cell metabolism to support viral replication and immune evasion.
  • The specific roles of SARS-CoV-2 accessory proteins, such as ORF7a, in metabolic reprogramming are not well understood.

Purpose of the Study:

  • To investigate the metabolic impact of the SARS-CoV-2 accessory protein ORF7a.
  • To elucidate the mechanisms by which ORF7a affects cellular metabolism, particularly mitochondrial function.

Main Methods:

  • Lentiviral expression of ORF7a in human lung epithelial (A549) and monocytic (THP1) cells.
  • Integrated transcriptomic, proteomic, and metabolomic analyses.
  • High-resolution respirometry and Blue Native-PAGE to assess mitochondrial respiratory function and complex assembly.

Main Results:

  • ORF7a significantly dysregulated glucose and lipid metabolism.
  • Impaired mitochondrial oxidative phosphorylation, reduced respiration, mitochondrial depolarization, and increased reactive oxygen species were observed.
  • ORF7a upregulated pyruvate dehydrogenase kinase 4 (PDK4), suppressing pyruvate oxidation, and caused complex I dysfunction and defective respiratory supercomplex assembly.

Conclusions:

  • SARS-CoV-2 ORF7a protein disrupts mitochondrial metabolism through enzymatic regulation and destabilization of the respiratory chain.
  • Mitochondria are a key target of SARS-CoV-2-induced metabolic reprogramming.
  • ORF7a's effects on mitochondrial function present potential therapeutic targets.
Keywords:
CP: microbiologyORF7aSARS-CoV-2complex I dysfunctionmetabolic reprogrammingmitochondrial dysfunctionoxidative phosphorylationrespiratory chain supercomplexes

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