In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-11-14)
Abstract:
Dysfunction of the oxidative phosphorylation (OXPHOS) system is a major cause of human disease and the cellular consequences are highly complex. Here, we present comparative analyses of mitochondrial proteomes, cellular transcriptomes and targeted metabolomics of five knockout mouse strains deficient in essential factors required for mitochondrial DNA gene expression, leading to OXPHOS dysfunction. Moreover, we describe sequential protein changes during post-natal development and progressive OXPHOS dysfunction in time course analyses in control mice and a middle lifespan knockout, respectively. Very unexpectedly, we identify a new response pathway to OXPHOS dysfunction in which the intra-mitochondrial synthesis of coenzyme Q (ubiquinone, Q) and Q levels are profoundly decreased, pointing towards novel possibilities for therapy. Our extensive omics analyses provide a high-quality resource of altered gene expression patterns under severe OXPHOS deficiency comparing several mouse models, that will deepen our understanding, open avenues for research and provide an important reference for diagnosis and treatment.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.30952.001
DOI:
10.7554/eLife.30952.002
DOI:
10.7554/eLife.30952.003
DOI:
10.7554/eLife.30952.007
DOI:
10.7554/eLife.30952.004
DOI:
10.7554/eLife.30952.005
DOI:
10.7554/eLife.30952.006
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10.7554/eLife.30952.008
DOI:
10.7554/eLife.30952.009
DOI:
10.7554/eLife.30952.010
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10.7554/eLife.30952.011
DOI:
10.7554/eLife.30952.012
DOI:
10.7554/eLife.30952.013
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10.7554/eLife.30952.015
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10.7554/eLife.30952.014
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10.7554/eLife.30952.016
DOI:
10.7554/eLife.30952.020
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10.7554/eLife.30952.017
DOI:
10.7554/eLife.30952.018
DOI:
10.7554/eLife.30952.019
DOI:
10.7554/eLife.30952.021
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10.7554/eLife.30952.022
DOI:
10.7554/eLife.30952.023
DOI:
10.7554/eLife.30952.024
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10.7554/eLife.30952.025
DOI:
10.7554/eLife.30952.026
DOI:
10.7554/eLife.30952.027
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10.7554/eLife.30952.028
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10.7554/eLife.30952.029
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10.7554/eLife.30952.031
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10.7554/eLife.30952.032
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10.7554/eLife.30952.030
DOI:
10.7554/eLife.30952.033
DOI:
10.7554/eLife.30952.034
DOI:
10.7554/eLife.30952.035
DOI:
10.7554/eLife.30952.036
DOI:
10.7554/eLife.30952.037
DOI:
10.7554/eLife.30952.038
DOI:
10.7554/eLife.30952.039
DOI:
10.7554/eLife.30952.040
DOI:
10.7554/eLife.30952.041
DOI:
10.7554/eLife.30952.042
DOI:
10.7554/eLife.30952.045
DOI:
10.7554/eLife.30952.046
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2017
detail.hit.zdb_id:
2687154-3