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.
Highlights
The membrane deforming dynamin family members MxA and MxB are large GTPases that convey resistance to a variety of infectious viruses
In addition to reported localization at nuclear pores, we find that MxB is intimately associated with the inner mitochondria, where it plays an essential role in the maintenance of mitochondrial cristae and DNA stability of this organelle
As the related family member MxA has been shown to convey a partial resistance to the hepatocyte-centric HBV33, while associating with membranous structures in hepatocytes, our goal is to compare the distribution and expression of the highly related family member MxB in hepatocyte cell lines and in the whole liver
Summary
The membrane deforming dynamin family members MxA and MxB are large GTPases that convey resistance to a variety of infectious viruses. 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. 1234567890():,; Mitochondria are dynamic organelles that undergo fission and fusion events in response to changes in metabolic needs and important cellular processes such as cell division and apoptosis[1,2,3] Central to these alterations in mitochondrial form are the dynamin family of large GTPases, which are known to bind and remodel membranes[4,5]. In addition to reported localization at nuclear pores, we find that MxB is intimately associated with the inner mitochondria, where it plays an essential role in the maintenance of mitochondrial cristae and DNA stability of this organelle
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