Atad3 function is essential for early post-implantation development in the mouse

PLoS One. 2013;8(1):e54799. doi: 10.1371/journal.pone.0054799. Epub 2013 Jan 25.

Abstract

The mitochondrial AAA+-ATPase ATAD3 is implicated in the regulation of mitochondrial and ER dynamics and was shown to be necessary for larval development in Caenorhabditis elegans. In order to elucidate the relevance of ATAD3 for mammalian development, the phenotype of an Atad3 deficient mouse line was analyzed. Atad3 deficient embryos die around embryonic day E7.5 due to growth retardation and a defective development of the trophoblast lineage immediately after implantation into the uterus. This indicates an essential function of Atad3 for the progression of the first steps of post-implantation development at a time point when mitochondrial biogenesis and ATP production by oxidative phosphorylation are required. Therefore, murine Atad3 plays an important role in the biogenesis of mitochondria in trophoblast stem cells and in differentiating trophoblasts. At the biochemical level, we report here that ATAD3 is present in five native mitochondrial protein complexes of different sizes, indicating complex roles of the protein in mitochondrial architecture and function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / metabolism
  • Alternative Splicing
  • Animals
  • Cell Differentiation
  • Embryonic Development / genetics*
  • Gene Expression Regulation, Developmental*
  • Gene Order
  • Genes, Lethal
  • Mice
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Molecular Weight
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Mutation
  • Protein Isoforms
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Trophoblasts / metabolism
  • Trophoblasts / pathology

Substances

  • Atad3a protein, mouse
  • Mitochondrial Proteins
  • Multiprotein Complexes
  • Protein Isoforms
  • Adenosine Triphosphatases
  • ATPases Associated with Diverse Cellular Activities

Grants and funding

This work was funded by the Deutsche Forschungsgemeinschaft (DFG, SFB704).