Actin and myosin contribute to mammalian mitochondrial DNA maintenance

A Reyes1, J He, C C Mao

  • 1MRC Mitochondrial Biology Unit, Cambridge, UK.

Nucleic Acids Research
|March 15, 2011
PubMed

Insights

The actomyosin cytoskeleton, including non-muscle myosin II and β-actin, is crucial for maintaining mitochondrial DNA (mtDNA) in mammalian cells. Disrupting these proteins affects mtDNA copy number and organization.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Mitochondrial DNA (mtDNA) maintenance is essential for cellular function.
  • The role of the cytoskeleton in mtDNA dynamics is increasingly recognized.
  • Budding yeast studies suggest a link between actin cytoskeleton and mtDNA segregation.

Purpose of the Study:

  • To investigate the involvement of actomyosin cytoskeleton proteins in mammalian mtDNA maintenance.
  • To identify specific cytoskeletal proteins associated with mitochondrial DNA.
  • To elucidate the functional consequences of actomyosin disruption on mtDNA.

Main Methods:

  • Proteomic analysis to identify proteins associated with rat liver mitochondrial DNA.
  • Gene silencing (siRNA) in human cells targeting MYH9 and MYH10 genes.
  • Genetic ablation in mouse embryonic fibroblasts.
  • Assessment of mitochondrial DNA copy number, topology, and organization.
  • Protease-protection assays and iodixanol gradient analysis.

Main Results:

  • Non-muscle myosin heavy chain IIA and β-actin were identified as tightly associated with mitochondrial DNA.
  • Silencing MYH9 or MYH10 in human cells altered mtDNA topology and increased copy number.
  • Simultaneous silencing of MYH9 and MYH10 further enhanced the increase in mtDNA copy number.
  • Genetic ablation of non-muscle myosin IIB in mouse cells decreased mtDNA copy number by 60%.
  • β-actin gene silencing also impacted mtDNA copy number and organization.
  • Evidence suggests β-actin and non-muscle myosin heavy chain IIA are present within mitochondria and associated with mtDNA.

Conclusions:

  • The actomyosin cytoskeleton, comprising non-muscle myosin II and β-actin, plays a significant role in mammalian mitochondrial DNA maintenance.
  • These cytoskeletal components are physically associated with mitochondrial DNA.
  • Disruption of the actomyosin network leads to alterations in mitochondrial DNA copy number and organization, highlighting its critical function.

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