Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population

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Serval ID
serval:BIB_6F0E16D7C845
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population
Journal
Cell
Author(s)
Wu Y., Williams E.G., Dubuis S., Mottis A., Jovaisaite V., Houten S.M., Argmann C.A., Faridi P., Wolski W., Kutalik Z., Zamboni N., Auwerx J., Aebersold R.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
09/2014
Peer-reviewed
Oui
Volume
158
Number
6
Pages
1415-1430
Language
english
Notes
IUMSP2014/09
Abstract
The manner by which genotype and environment affect complex phenotypes is one of the fundamental questions in biology. In this study, we quantified the transcriptome--a subset of the metabolome--and, using targeted proteomics, quantified a subset of the liver proteome from 40 strains of the BXD mouse genetic reference population on two diverse diets. We discovered dozens of transcript, protein, and metabolite QTLs, several of which linked to metabolic phenotypes. Most prominently, Dhtkd1 was identified as a primary regulator of 2-aminoadipate, explaining variance in fasted glucose and diabetes status in both mice and humans. These integrated molecular profiles also allowed further characterization of complex pathways, particularly the mitochondrial unfolded protein response (UPR(mt)). UPR(mt) shows strikingly variant responses at the transcript and protein level that are remarkably conserved among C. elegans, mice, and humans. Overall, these examples demonstrate the value of an integrated multilayered omics approach to characterize complex metabolic phenotypes.
Pubmed
Web of science
Open Access
Yes
Create date
30/10/2014 9:15
Last modification date
20/08/2019 14:28
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