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Published on: January 11, 2017
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.
Abstract:
The membrane deforming dynamin family members MxA and MxB are large GTPases that convey resistance to a variety of infectious viruses. During viral infection, Mx proteins are known to show markedly increased expression via an interferon-responsive promoter to associate with nuclear pores. In this study we report that MxB is an inner mitochondrial membrane GTPase that plays an important role in the morphology and function of this organelle. Expression of mutant MxB or siRNA knockdown of MxB leads to fragmented mitochondria with disrupted inner membranes that are unable to maintain a proton gradient, while expelling their nucleoid-based genome into the cytoplasm. These findings implicate a dynamin family member in mitochondrial-based changes frequently observed during an interferon-based, anti-viral response.
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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