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Role of Mitochondrial Dynamics in Microglial Activation and Metabolic Switch

Alejandro Montilla1,2, Asier Ruiz1,2, Mar Marquez1

  • 1Achucarro Basque Center for Neuroscience and Department of Neuroscience, University of the Basque Country, Leioa, Spain.

Immunohorizons
|August 11, 2021
PubMed

Insights

Microglia metabolic reprogramming during inflammation involves mitochondrial changes. While Drp1-dependent fission impacts activation markers, it does not drive the core metabolic switch or repolarization in activated microglia.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Immunology

Background:

  • Microglia, the brain's immune cells, maintain homeostasis but can adopt a proinflammatory phenotype during injury.
  • This activation involves metabolic reprogramming, shifting towards glycolysis and reduced oxidative phosphorylation.
  • Understanding these metabolic shifts is crucial for addressing neuroinflammatory diseases.

Purpose of the Study:

  • To investigate the role of mitochondrial dynamics, specifically fission, in microglial metabolic reprogramming.
  • To determine if inhibiting mitochondrial fission affects the proinflammatory phenotype and metabolic state of activated microglia.

Main Methods:

  • Primary rat microglia were stimulated with lipopolysaccharide (LPS) plus interferon-gamma (IFN-γ) to induce a proinflammatory state.
  • Mitochondrial membrane potential was assessed.
  • The effect of mitochondrial division inhibitor-1 (Mdivi-1), a Drp1 inhibitor, on microglial activation and metabolism was examined.

Main Results:

  • Microglia stimulated with LPS plus IFN-γ exhibited suppressed oxidative phosphorylation but maintained mitochondrial membrane potential.
  • Reverse operation of F0F1-ATP synthase was identified as contributing to mitochondrial membrane potential.
  • Mdivi-1 treatment reduced proinflammatory markers but did not restore oxidative phosphorylation or repolarize microglia.

Conclusions:

  • Drp1-dependent mitochondrial fission is involved in microglial activation but is not essential for the metabolic reprogramming or repolarization of microglia.
  • The metabolic switch in activated microglia is complex and not solely regulated by mitochondrial fission.

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