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Macrophage mitochondrial MFN2 (mitofusin 2) links immune stress and immune response through reactive oxygen species

Jorge Lloberas1, Juan P Muñoz2,3,4, María Isabel Hernández-Álvarez2,3,4

  • 1Macrophage Biology Group, Department of Cell Biology, Physiology and Immunology, Facultat de Biologia, Universitat de Barcelona , Barcelona, Spain.

Autophagy
|November 10, 2020
PubMed

Insights

Mitofusin 2 (MFN2) is crucial for macrophage immune responses by enabling reactive oxygen species (ROS) production. Its deficiency impairs immunity against infections and inflammation.

Area of Science:

  • Immunology
  • Cell Biology
  • Mitochondrial Biology

Background:

  • Mitofusin 2 (MFN2) is known for its role in mitochondrial fusion and endoplasmic reticulum interactions.
  • The specific function of MFN2 in macrophage immune responses remains incompletely understood.

Purpose of the Study:

  • To investigate the role of MFN2 in macrophage function and its impact on immunity.
  • To determine if MFN2 is essential for reactive oxygen species (ROS) production in macrophages.

Main Methods:

  • Utilized myeloid-conditional knockout (KO) mice models lacking MFN2.
  • Assessed mitochondrial respiration, ROS production, cytokine induction, and immune cell functions.
  • Evaluated immune responses in models of non-septic inflammation, Listeria infection, Mycobacterium tuberculosis infection, and LPS endotoxemia.

Main Results:

  • MFN2, but not MFN1, is essential for adapting mitochondrial respiration to stress and for ROS production in macrophages.
  • MFN2 deficiency led to impaired ROS production, affecting cytokine and nitric oxide induction.
  • Lack of MFN2 resulted in dysfunctional autophagy, apoptosis, phagocytosis, and antigen processing.
  • MFN2-deficient macrophages showed impaired responses in inflammation and failed to provide protection against bacterial infections and endotoxemia.

Conclusions:

  • MFN2 plays a critical, unexpected role in ROS production within macrophages.
  • MFN2 is vital for both natural and acquired immunity, influencing the overall immune response.
Keywords:
AutophagyROSbactericidal activitycytokineinflammationmacrophagesphagocytosis

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