The SARS-CoV-2 spike glycoprotein interacts with MAO-B and impairs mitochondrial energetics

Chantal A. Pileggi; Gaganvir Parmar; Hussein Elkhatib; Corina M. Stewart; Irina Alecu; Marceline Côté; Steffany A.L. Bennett; Jagdeep K. Sandhu; Miroslava Cuperlovic-Culf; Mary-Ellen Harper

Current Research in Neurobiology (Jan 2023)

The SARS-CoV-2 spike glycoprotein interacts with MAO-B and impairs mitochondrial energetics

Chantal A. Pileggi,
Gaganvir Parmar,
Hussein Elkhatib,
Corina M. Stewart,
Irina Alecu,
Marceline Côté,
Steffany A.L. Bennett,
Jagdeep K. Sandhu,
Miroslava Cuperlovic-Culf,
Mary-Ellen Harper

Affiliations

Chantal A. Pileggi: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, ON, K1H 8M5, Canada; National Research Council of Canada, Digital Technologies Research Centre, 1200 Montreal Road, Ottawa, ON, K1A 0R6, Canada
Gaganvir Parmar: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, ON, K1H 8M5, Canada
Hussein Elkhatib: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, ON, K1H 8M5, Canada
Corina M. Stewart: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, ON, K1H 8M5, Canada; Current Address: Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
Irina Alecu: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, ON, K1H 8M5, Canada; Neural Regeneration Laboratory, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada
Marceline Côté: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, ON, K1H 8M5, Canada; Centre for Infection, Immunity and Inflammation, University of Ottawa, ON, K1H 8M5, Canada
Steffany A.L. Bennett: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, ON, K1H 8M5, Canada; Neural Regeneration Laboratory, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada
Jagdeep K. Sandhu: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, ON, K1H 8M5, Canada; Centre for Infection, Immunity and Inflammation, University of Ottawa, ON, K1H 8M5, Canada; Human Health Therapeutics Research Centre, National Research Council Canada, 1200 Montreal Road, Ottawa, ON, K1A 0R6, Canada
Miroslava Cuperlovic-Culf: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, ON, K1H 8M5, Canada; National Research Council of Canada, Digital Technologies Research Centre, 1200 Montreal Road, Ottawa, ON, K1A 0R6, Canada
Mary-Ellen Harper: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, ON, K1H 8M5, Canada; Centre for Infection, Immunity and Inflammation, University of Ottawa, ON, K1H 8M5, Canada; Corresponding author. Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.

Journal volume & issue: Vol. 5
p. 100112

Abstract

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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.

Published in Current Research in Neurobiology

ISSN: 2665-945X (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/current-research-in-neurobiology/

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