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Norway

PMID:21118999  

NOA1 is an essential GTPase required for mitochondrial protein synthesis.

Mateusz Kolanczyk | Markus Pech | Tomasz Zemojtel | Hiroshi Yamamoto | Ivan Mikula | Maria-Antonietta Calvaruso | Mariël van den Brand | Ricarda Richter | Bjoern Fischer | Anita Ritz | Nadine Kossler | Boris Thurisch | Ralf Spoerle | Jan Smeitink | Uwe Kornak | Danny Chan | Martin Vingron | Pavel Martasek | Robert N Lightowlers | Leo Nijtmans | Markus Schuelke | Knud H Nierhaus | Stefan Mundlos
Molecular biology of the cell | 2011

Nitric oxide associated-1 (NOA1) is an evolutionarily conserved guanosine triphosphate (GTP) binding protein that localizes predominantly to mitochondria in mammalian cells. On the basis of bioinformatic analysis, we predicted its possible involvement in ribosomal biogenesis, although this had not been supported by any experimental evidence. Here we determine NOA1 function through generation of knockout mice and in vitro assays. NOA1-deficient mice exhibit midgestation lethality associated with a severe developmental defect of the embryo and trophoblast. Primary embryonic fibroblasts isolated from NOA1 knockout embryos show deficient mitochondrial protein synthesis and a global defect of oxidative phosphorylation (OXPHOS). Additionally, Noa1⁻/⁻ cells are impaired in staurosporine-induced apoptosis. The analysis of mitochondrial ribosomal subunits from Noa1⁻/⁻ cells by sucrose gradient centrifugation and Western blotting showed anomalous sedimentation, consistent with a defect in mitochondrial ribosome assembly. Furthermore, in vitro experiments revealed that intrinsic NOA1 GTPase activity was stimulated by bacterial ribosomal constituents. Taken together, our data show that NOA1 is required for mitochondrial protein synthesis, likely due to its yet unidentified role in mitoribosomal biogenesis. Thus, NOA1 is required for such basal mitochondrial functions as adenosine triphosphate (ATP) synthesis and apoptosis.

Pubmed ID: 21118999

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Associated grants

  • Agency: Wellcome Trust, United Kingdom
    Id: 074454
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/F011520/1

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RRID:CVCL_0030

Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens

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