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          Institute: MPI für molekulare Genetik     Collection: Department of Computational Molecular Biology     Display Documents



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ID: 538382.0, MPI für molekulare Genetik / Department of Computational Molecular Biology
NOA1 is an essential GTPase required for mitochondrial protein synthesis
Authors:Kolanczyk, Mateusz; Pech, Markus; Zemojte, Tomasz; Yamamoto, Hiroshi; Mikula, Ivan; Calvaruso, Maria-Antonietta; van den Brand, Mariel; 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
Language:English
Date of Publication (YYYY-MM-DD):2011-01-01
Title of Journal:Molecular Biology of the Cell
Journal Abbrev.:Mol Biol Cell
Volume:22
Issue / Number:1
Start Page:1
End Page:11
Copyright:© 2011 by The American Society for Cell Biology
Review Status:not specified
Audience:Experts Only
Abstract / Description:NOA1 is an evolutionarily conserved GTP binding protein, which localizes predominantly to mitochondria in mammalian cells. Based on 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 knock-out mice and in-vitro assays. NOA1 deficient mice exhibit mid-gestation lethality associated with a severe developmental defect of the embryo and trophoblast. Primary embryonic fibroblasts isolated from NOA1 knock-out 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. Further, 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 ATP synthesis and apoptosis.
External Publication Status:published
Document Type:Article
Communicated by:Martin Vingron
Affiliations:MPI für molekulare Genetik
External Affiliations:Institute for Medical Genetics, Charitè, Universitätsmedizin, 13353 Berlin, Germany
Department of Pediatrics and Center for Applied Genomics, Ist Faculty of Medicine, Charles
University, 12109 Prague, Czech Republic
Nijmegen Centre for Mitochondrial Disorders at the Department of Pediatrics, Radboud
University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, Netherlands
Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University,
Framlington Place, Newcastle upon Tyne, UK NE2 4HH
Department of Biochemistry, the University of Hong Kong, Hong Kong, China
Department of Neuropediatrics and NeuroCure Clinical Research Center, Charité University
Medical Center, 13353 Berlin, Germany
Identifiers:URL:http://www.molbiolcell.org/cgi/content/abstract/mb... [ID No:1]
DOI:10.1091/mbc.E10-07-0643 [ID No:2]
ISSN:1059-1524 [ID No:3]
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