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Mitochondrial Dysfunction: A Prelude to Neuropathogenesis of SARS-CoV-2

Artem Pliss1, Andrey N Kuzmin1, Paras N Prasad1

  • 1Institute for Lasers, Photonics and Biophotonics and Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, New York 14260, United States.

ACS Chemical Neuroscience
|January 20, 2022
PubMed

Insights

SARS-CoV-2 infection impairs brain microglia mitochondria, reducing mitochondrial DNA and increasing lipid saturation. This suggests new therapeutic targets for neuro-COVID.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • SARS-CoV-2 exhibits neuroinvasive properties, leading to neurological conditions.
  • Mitochondrial dysfunction in brain microglia is a key factor in SARS-CoV-2 neuropathology.
  • The specific biochemical changes in mitochondria driving neuro-COVID progression are not well understood.

Purpose of the Study:

  • To molecularly profile mitochondria in SARS-CoV-2-infected microglia using Raman microspectrometry.
  • To characterize the biochemical alterations within microglia mitochondria during SARS-CoV-2 infection.
  • To understand the molecular basis of mitochondrial dysfunction in neuro-COVID.

Main Methods:

  • Utilized Raman microspectrometry for molecular profiling of single cellular organelles.
  • Analyzed microglia cells treated with SARS-CoV-2 spike protein or heat-inactivated virus.
  • Compared molecular changes in mitochondria, Golgi apparatus, and lipid droplets.

Main Results:

  • Observed a significant reduction in mitochondrial DNA (mtDNA) content in treated microglia.
  • Detected an increase in phospholipid saturation levels within mitochondria.
  • Found no significant changes in the Golgi apparatus or lipid droplets.

Conclusions:

  • Microglia mitochondrial dysfunction, characterized by mtDNA reduction and altered lipid saturation, is a key feature of SARS-CoV-2 infection.
  • Increased reactive oxygen species synthesis is hypothesized to drive these mitochondrial transformations.
  • Mitochondria-targeted therapies are proposed as a strategy to mitigate SARS-CoV-2-induced neuropathology.
Keywords:
MicrogliaROSRaman spectrometrySARS-CoV-2mitochondrianeuro-COVID

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