Systems proteomics of liver mitochondria function.
Recent improvements in quantitative proteomics approaches, including Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS), permit reproducible large-scale protein measurements across diverse cohorts. Together with genomics, transcriptomics, and other technologies, transomic data sets can be generated that permit detailed analyses across broad molecular interaction networks. Here, we examine mitochondrial links to liver metabolism through the genome, transcriptome, proteome, and metabolome of 386 individuals in the BXD mouse reference population. Several links were validated between genetic variants toward transcripts, proteins, metabolites, and phenotypes. Among these, sequence variants in Cox7a2l alter its protein's activity, which in turn leads to downstream differences in mitochondrial supercomplex formation. This data set demonstrates that the proteome can now be quantified comprehensively, serving as a key complement to transcriptomics, genomics, and metabolomics--a combination moving us forward in complex trait analysis.
Laboratory of Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, CH-1015, Switzerland. These authors contributed equally to this work.
Evan G
EG
Williams
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, CH-8093, Switzerland. These authors contributed equally to this work.
Yibo
Y
Wu
Laboratory of Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, CH-1015, Switzerland.
Pooja
P
Jha
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, CH-8093, Switzerland.
Sébastien
S
Dubuis
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, CH-8093, Switzerland.
Peter
P
Blattmann
Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1498, New York, NY 10029, USA.
Carmen A
CA
Argmann
Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1498, New York, NY 10029, USA.
Sander M
SM
Houten
Laboratory of Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, CH-1015, Switzerland.
Tiffany
T
Amariuta
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, CH-8093, Switzerland.
Witold
W
Wolski
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, CH-8093, Switzerland.
Nicola
N
Zamboni
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, CH-8093, Switzerland. Faculty of Science, University of Zurich, CH-8057, Switzerland. admin.auwerx@epfl.ch aebersold@imsb.biol.ethz.ch.
Ruedi
R
Aebersold
Laboratory of Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, CH-1015, Switzerland. admin.auwerx@epfl.ch aebersold@imsb.biol.ethz.ch.
Johan
J
Auwerx
D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D004032:Diet; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D014644:Genetic Variation; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D055442:Metabolome; D055432:Metabolomics; D051379:Mice; D008815:Mice, Inbred Strains; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D020543:Proteome; D040901:Proteomics; D040641:Quantitative Trait Loci; D059467:Transcriptome
D020543:Proteome; D002784:Cholesterol; C514296:Cox7a2 protein, mouse; D003576:Electron Transport Complex IV