The anti-viral dynamin family member MxB participates in mitochondrial integrity

Hong Cao1,2, E W Krueger2, Jing Chen2

  • 1Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.

Nature Communications
|February 28, 2020
PubMed

Insights

MxB, a dynamin family GTPase, is identified as an inner mitochondrial membrane protein crucial for organelle function. Its dysfunction causes mitochondrial fragmentation and genome expulsion, linking dynamins to antiviral responses.

Area of Science:

  • Cell Biology
  • Virology
  • Biochemistry

Background:

  • Dynamin family GTPases, including MxA and MxB, confer resistance to viral infections.
  • Mx proteins are upregulated during viral infections, localizing to nuclear pores.
  • The specific role of MxB in cellular organelles beyond viral defense remains largely uncharacterized.

Purpose of the Study:

  • To investigate the subcellular localization and function of MxB.
  • To determine the impact of MxB dysfunction on mitochondrial morphology and bioenergetics.
  • To explore the potential role of MxB in the cellular antiviral response.

Main Methods:

  • Subcellular localization studies using MxB expression.
  • Mitochondrial morphology assessment via microscopy.
  • Analysis of mitochondrial membrane potential and genome integrity.
  • RNA interference (siRNA) mediated knockdown of MxB.

Main Results:

  • MxB localizes to the inner mitochondrial membrane.
  • MxB dysfunction results in mitochondrial fragmentation and inner membrane disruption.
  • Impaired mitochondria exhibit a loss of proton gradient and expulsion of nucleoid DNA.
  • siRNA knockdown of MxB phenocopies the effects of MxB mutants.

Conclusions:

  • MxB is an inner mitochondrial membrane GTPase essential for maintaining mitochondrial morphology and function.
  • MxB plays a critical role in mitochondrial integrity, including genome maintenance.
  • These findings suggest a novel role for dynamin family members in the mitochondrial aspects of the interferon-mediated antiviral response.

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