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NOA1 is an essential GTPase required for mitochondrial protein synthesis

Lookup NU author(s): Professor Robert Lightowlers

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Abstract

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.

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Author(s): Kolanczyk M, Pech M, Zemojtel T, Yamamoto H, Mikula I, Calvaruso MA, 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 RN, Nijtmans L, Schuelke M, Nierhaus KH, Mundlos S

Publication type: Article

Publication status: Published

Journal: Molecular Biology of the Cell

Year: 2011

Volume: 22

Issue: 1

Pages: 1-11

Print publication date: 01/01/2011

ISSN (print): 1059-1524

ISSN (electronic): 1939-4586

Publisher: American Society for Cell Biology

URL: http://dx.doi.org/10.1091/mbc.E10-07-0643

DOI: 10.1091/mbc.E10-07-0643

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