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Nat Biotechnol. 2016 Nov;34(11):1191-1197. doi: 10.1038/nbt.3683. Epub 2016 Sep 26.

Mitochondrial protein functions elucidated by multi-omic mass spectrometry profiling.

Author information

1
Morgridge Institute for Research, Madison, Wisconsin, USA.
2
Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
3
Genome Center of Wisconsin, Madison, Wisconsin, USA.
4
Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
5
Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
#
Contributed equally

Abstract

Mitochondrial dysfunction is associated with many human diseases, including cancer and neurodegeneration, that are often linked to proteins and pathways that are not well-characterized. To begin defining the functions of such poorly characterized proteins, we used mass spectrometry to map the proteomes, lipidomes, and metabolomes of 174 yeast strains, each lacking a single gene related to mitochondrial biology. 144 of these genes have human homologs, 60 of which are associated with disease and 39 of which are uncharacterized. We present a multi-omic data analysis and visualization tool that we use to find covariance networks that can predict molecular functions, correlations between profiles of related gene deletions, gene-specific perturbations that reflect protein functions, and a global respiration deficiency response. Using this multi-omic approach, we link seven proteins including Hfd1p and its human homolog ALDH3A1 to mitochondrial coenzyme Q (CoQ) biosynthesis, an essential pathway disrupted in many human diseases. This Resource should provide molecular insights into mitochondrial protein functions.

PMID:
27669165
PMCID:
PMC5101133
DOI:
10.1038/nbt.3683
[Indexed for MEDLINE]
Free PMC Article

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