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SARS-CoV-2 Nsp8 induces mitophagy by damaging mitochondria

Shan Zong1, Yan Wu2, Weiling Li1

  • 1Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, 430056, China.

Virologica Sinica
|May 8, 2023
PubMed

Insights

The SARS-CoV-2 Nsp8 protein disrupts autophagy by blocking autophagosome-lysosome fusion and initiating incomplete mitophagy, damaging host cell mitochondria. This finding offers new insights into COVID-19's mechanisms and potential treatments.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Autophagy is crucial for host-pathogen interactions.
  • SARS-CoV-2 disrupts cellular autophagy, but the mechanism remains unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism by which SARS-CoV-2 affects autophagy.
  • To investigate the role of SARS-CoV-2 Nsp8 protein in this process.

Main Methods:

  • Immunofluorescence assays to observe protein localization and autophagosome accumulation.
  • Experiments to analyze the interaction between Nsp8, mitochondria, autophagosomes, and lysosomes.

Main Results:

  • SARS-CoV-2 Nsp8 prevents autophagosome-lysosome fusion, leading to autophagosome accumulation.
  • Nsp8 localizes to mitochondria, initiating mitophagy.
  • Nsp8 induces incomplete mitophagy, with distinct roles for its N-terminal and C-terminal domains.

Conclusions:

  • Nsp8 promotes mitochondrial damage and incomplete mitophagy.
  • This study expands understanding of SARS-CoV-2's impact on host cells.
  • Identifies Nsp8 as a potential target for novel therapeutic strategies against COVID-19.
Keywords:
AutophagyMitochondrial damageMitophagyNsp8SARS-CoV-2

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