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NOA1 is an essential GTPase required for mitochondrial protein synthesis
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 b...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016967/ https://www.ncbi.nlm.nih.gov/pubmed/21118999 http://dx.doi.org/10.1091/mbc.E10-07-0643 |
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author | Kolanczyk, Mateusz Pech, Markus Zemojtel, Tomasz Yamamoto, Hiroshi Mikula, Ivan Calvaruso, Maria-Antonietta van den Brand, Mariël Richter, Ricarda Fischer, Bjoern Ritz, Anita Kossler, Nadine Thurisch, Boris Spoerle, Ralf Smeitink, Jan Kornak, Uwe Chan, Danny Vingron, Martin Martasek, Pavel Lightowlers, Robert N. Nijtmans, Leo Schuelke, Markus Nierhaus, Knud H. Mundlos, Stefan |
author_facet | Kolanczyk, Mateusz Pech, Markus Zemojtel, Tomasz Yamamoto, Hiroshi Mikula, Ivan Calvaruso, Maria-Antonietta van den Brand, Mariël Richter, Ricarda Fischer, Bjoern Ritz, Anita Kossler, Nadine Thurisch, Boris Spoerle, Ralf Smeitink, Jan Kornak, Uwe Chan, Danny Vingron, Martin Martasek, Pavel Lightowlers, Robert N. Nijtmans, Leo Schuelke, Markus Nierhaus, Knud H. Mundlos, Stefan |
author_sort | Kolanczyk, Mateusz |
collection | PubMed |
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. |
format | Text |
id | pubmed-3016967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-30169672011-03-16 NOA1 is an essential GTPase required for mitochondrial protein synthesis Kolanczyk, Mateusz Pech, Markus Zemojtel, Tomasz Yamamoto, Hiroshi Mikula, Ivan Calvaruso, Maria-Antonietta van den Brand, Mariël Richter, Ricarda Fischer, Bjoern Ritz, Anita Kossler, Nadine Thurisch, Boris Spoerle, Ralf Smeitink, Jan Kornak, Uwe Chan, Danny Vingron, Martin Martasek, Pavel Lightowlers, Robert N. Nijtmans, Leo Schuelke, Markus Nierhaus, Knud H. Mundlos, Stefan Mol Biol Cell Articles 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. The American Society for Cell Biology 2011-01-01 /pmc/articles/PMC3016967/ /pubmed/21118999 http://dx.doi.org/10.1091/mbc.E10-07-0643 Text en © 2011 Kolanczyk et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,“ “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Kolanczyk, Mateusz Pech, Markus Zemojtel, Tomasz Yamamoto, Hiroshi Mikula, Ivan Calvaruso, Maria-Antonietta van den Brand, Mariël Richter, Ricarda Fischer, Bjoern Ritz, Anita Kossler, Nadine Thurisch, Boris Spoerle, Ralf Smeitink, Jan Kornak, Uwe Chan, Danny Vingron, Martin Martasek, Pavel Lightowlers, Robert N. Nijtmans, Leo Schuelke, Markus Nierhaus, Knud H. Mundlos, Stefan NOA1 is an essential GTPase required for mitochondrial protein synthesis |
title | NOA1 is an essential GTPase required for mitochondrial protein synthesis |
title_full | NOA1 is an essential GTPase required for mitochondrial protein synthesis |
title_fullStr | NOA1 is an essential GTPase required for mitochondrial protein synthesis |
title_full_unstemmed | NOA1 is an essential GTPase required for mitochondrial protein synthesis |
title_short | NOA1 is an essential GTPase required for mitochondrial protein synthesis |
title_sort | noa1 is an essential gtpase required for mitochondrial protein synthesis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016967/ https://www.ncbi.nlm.nih.gov/pubmed/21118999 http://dx.doi.org/10.1091/mbc.E10-07-0643 |
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