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Updated: Jul 9, 2025
Author Spotlight: Decoding Mitochondrial Aging
Published on: June 30, 2023
The SARS-CoV-2 spike glycoprotein interacts with MAO-B and impairs mitochondrial energetics
Chantal A Pileggi1,2,3, Gaganvir Parmar1,2, Hussein Elkhatib1,2
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Abstract:
SARS-CoV-2 infection is associated with both acute and post-acute neurological symptoms. Emerging evidence suggests that SARS-CoV-2 can alter mitochondrial metabolism, suggesting that changes in brain metabolism may contribute to the development of acute and post-acute neurological complications. Monoamine oxidase B (MAO-B) is a flavoenzyme located on the outer mitochondrial membrane that catalyzes the oxidative deamination of monoamine neurotransmitters. Computational analyses have revealed high similarity between the SARS-CoV-2 spike glycoprotein receptor binding domain on the ACE2 receptor and MAO-B, leading to the hypothesis that SARS-CoV-2 spike glycoprotein may alter neurotransmitter metabolism by interacting with MAO-B. Our results empirically establish that the SARS-CoV-2 spike glycoprotein interacts with MAO-B, leading to increased MAO-B activity in SH-SY5Y neuron-like cells. Common to neurodegenerative disease pathophysiological mechanisms, we also demonstrate that the spike glycoprotein impairs mitochondrial bioenergetics, induces oxidative stress, and perturbs the degradation of depolarized aberrant mitochondria through mitophagy. Our findings also demonstrate that SH-SY5Y neuron-like cells expressing the SARS-CoV-2 spike protein were more susceptible to MPTP-induced necrosis, likely necroptosis. Together, these results reveal novel mechanisms that may contribute to SARS-CoV-2-induced neurodegeneration.
Insights
The SARS-CoV-2 spike protein interacts with Monoamine Oxidase B (MAO-B), increasing its activity and impairing mitochondrial function. This may explain neurological symptoms seen in COVID-19 patients and contribute to neurodegeneration.
Area of Science:
- Neuroscience
- Virology
- Biochemistry
Background:
- SARS-CoV-2 infection causes acute and post-acute neurological symptoms.
- Altered brain metabolism is a potential contributor to these neurological complications.
- Monoamine oxidase B (MAO-B) is crucial for neurotransmitter metabolism.
Purpose of the Study:
- To investigate the interaction between SARS-CoV-2 spike glycoprotein and MAO-B.
- To determine the impact of this interaction on neuronal metabolism and function.
- To elucidate mechanisms underlying SARS-CoV-2-induced neurodegeneration.
Main Methods:
- Computational analysis to identify potential interactions.
- In vitro experiments using SH-SY5Y neuron-like cells.
- Assays to measure MAO-B activity, mitochondrial bioenergetics, oxidative stress, and mitophagy.
- Assessment of cell susceptibility to MPTP-induced cell death.
Main Results:
- SARS-CoV-2 spike glycoprotein directly interacts with MAO-B, increasing its activity.
- Spike glycoprotein impairs mitochondrial bioenergetics and induces oxidative stress.
- Mitophagy, the degradation of damaged mitochondria, was perturbed.
- Cells expressing spike protein showed increased susceptibility to MPTP-induced necrosis/necroptosis.
Conclusions:
- SARS-CoV-2 spike glycoprotein interaction with MAO-B is a novel mechanism contributing to neurodegeneration.
- Impaired mitochondrial function and oxidative stress are key consequences.
- These findings offer insights into the neurological complications of COVID-19.
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