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          Institute: MPI für molekulare Genetik     Collection: Research Group Development and Disease     Display Documents



ID: 538378.0, MPI für molekulare Genetik / Research Group Development and Disease
NOA1 is an essential GTPase required for mitochondrial protein synthesis
Authors:Kolanczyk, M.; Pech, M.; Zemojtel, T.; Yamamoto, H.; Mikula, I.; Calvaruso, M. A.; van den Brand, M.; Richter, R.; Fischer, B.; Ritz, A.; Kossler, N.; Thurisch, B.; Spoerle, R.; Smeitink, J.; Kornak, U.; Chan, D.; Vingron, M.; Martasek, P.; Lightowlers, R. N.; Nijtmans, L.; Schuelke, M.; Nierhaus, K. H.; Mundlos, S.
Date of Publication (YYYY-MM-DD):2011-01-01
Title of Journal:Mol Biol Cell
Volume:22
Issue / Number:1
Start Page:1
End Page:11
Audience:Not Specified
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Communicated by:Stefan Mundlos
Affiliations:MPI für molekulare Genetik
External Affiliations:%G eng
Identifiers:ISSN:1939-4586 (Electronic) 1059-1524 (Linking) %R mbc.... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/21118999 [ID No:2]
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