NOA1 is an essential GTPase required for mitochondrial protein synthesis.
Publication year
2011Author(s)
Source
Molecular Biology of the Cell, 22, 1, (2011), pp. 1-11ISSN
Publication type
Article / Letter to editor
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Organization
PI Group Neurobiology of Language
Paediatrics - OUD tm 2017
Laboratory of Genetic, Endocrine and Metabolic Diseases
Former Organization
F.C. Donders Centre for Cognitive Neuroimaging
Journal title
Molecular Biology of the Cell
Volume
vol. 22
Issue
iss. 1
Page start
p. 1
Page end
p. 11
Subject
110 000 Neurocognition of Language; IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism; IGMD 8: Mitochondrial medicine NCMLS 5: Membrane transport and intracellular motility; IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolismAbstract
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.
This item appears in the following Collection(s)
- Academic publications [238441]
- Donders Centre for Cognitive Neuroimaging [3824]
- Electronic publications [122508]
- Faculty of Medical Sciences [90373]
- Open Access publications [97504]
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