Comparison of Mitochondrial Response to SARS-CoV-2 Spike Protein Receptor Binding Domain in Human Lung Microvascular, Coronary Artery Endothelial, and Bronchial Epithelial Cells

The study “Comparison of Mitochondrial Response to SARS-CoV-2 Spike Protein Receptor Binding Domain in Human Lung Microvascular, Coronary Artery Endothelial, and Bronchial Epithelial Cells” provides important insights into the effects of the SARS-CoV-2 receptor binding domain (RBD) on different cell types.

Here’s a summary:

  1. Study Focus: The research examined the impact of the SARS-CoV-2 RBD on the mitochondrial network, cristae morphology, oxygen consumption, production of mitochondrial reactive oxygen species (mitoROS), and inflammatory cytokine expression in human lung microvascular endothelial cells (HLMVEC), coronary artery endothelial cells (HCAEC), and bronchial epithelial cells (HBEC)​​.
  2. Key Findings:
    • Mitochondrial Morphology Changes: In HLMVEC, SCoV2-RBD treatment caused significant fragmentation of the mitochondrial network, including decreased mitochondrial area, branch length, and network branches. No such changes were observed in HCAEC and HBEC​​.
    • Intercristae Distance: The intercristae distance in SCoV2-RBD-primed HLMVEC increased significantly, indicating structural alterations within the mitochondria. Again, no such changes were observed in HCAEC and HBEC​​.
    • Mitochondrial and Glycolytic Activity: SCoV2-RBD significantly suppressed mitochondrial respiration and glycolysis in HLMVEC, suggesting impaired mitochondrial function. No substantial changes were noted in HCAEC and HBEC​​.
    • mitoROS Production: Treatment with SCoV2-RBD induced mitoROS production in HLMVEC and HCAEC, but not in HBEC. This indicates differential sensitivity to oxidative stress among these cell types​​.
    • Impact of mitoROS on Mitochondrial Morphology: Using a mitochondrial superoxide scavenger, the study found that mitoROS influenced the mitochondrial network changes in HLMVEC, suggesting a role in the observed mitochondrial fragmentation​​.
    • Inflammatory Cytokines and mitoROS: SCoV2-RBD treatment resulted in significant cytokine upregulation in all cell lines. The addition of the mitoROS scavenger reversed these changes, indicating that mitoROS are key regulators of inflammation induced by SCoV2-RBD​​.
  3. Conclusions and Implications:
    • The study revealed exclusive sensitivity of HLMVEC mitochondria to SCoV2-RBD, leading to fragmentation and reduced mitochondrial volume. It suggests that cell interaction with SCoV2-RBD affects mitochondrial respiratory chain efficiency by destabilizing mitochondrial structures.
    • The findings indicate that mitochondrial ROS are crucial in mediating the inflammatory response to SCoV2-RBD, particularly in endothelial and epithelial cells.
    • The study supports the potential of mitoROS scavengers or antioxidants as therapeutics to prevent severe complications during coronavirus infections​​.

This research underscores the cell type-specific impact of SARS-CoV-2 on mitochondrial function and highlights the importance of considering mitochondrial dynamics and ROS in understanding and treating COVID-19-related complications.

Read More: https://www.biorxiv.org/content/10.1101/2023.12.19.572363v1.full.pdf

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