Reference : Multilayered genetic and omics dissection of mitochondrial activity in a mouse refere...
Scientific journals : Article
Life sciences : Genetics & genetic processes
Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population.
Wu, Yibo [> >]
Williams, Evan mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Dubuis, Sebastien [> >]
Mottis, Adrienne [> >]
Jovaisaite, Virginija [> >]
Houten, Sander M. [> >]
Argmann, Carmen A. [> >]
Faridi, Pouya [> >]
Wolski, Witold [> >]
Kutalik, Zoltan [> >]
Zamboni, Nicola [> >]
Auwerx, Johan [> >]
Aebersold, Ruedi [> >]
Yes (verified by ORBilu)
United States
[en] Animals ; Gene Expression Profiling ; Glucose/metabolism ; Humans ; Ketone Oxidoreductases/metabolism ; Liver/chemistry/cytology/metabolism ; Mice/classification/genetics/metabolism ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mitochondria/chemistry/metabolism ; Proteome/analysis ; Quantitative Trait Loci ; Serum/chemistry/metabolism ; Unfolded Protein Response
[en] 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.
Copyright (c) 2014 Elsevier Inc. All rights reserved.

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