Mitochondrial protein functions elucidated by multi-omic mass spectrometry profiling.
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.
Morgridge Institute for Research, Madison, Wisconsin, USA.|Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Jonathan A
JA
Stefely
Genome Center of Wisconsin, Madison, Wisconsin, USA.|Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Nicholas W
NW
Kwiecien
Genome Center of Wisconsin, Madison, Wisconsin, USA.|Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Elyse C
EC
Freiberger
Genome Center of Wisconsin, Madison, Wisconsin, USA.|Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Alicia L
AL
Richards
Morgridge Institute for Research, Madison, Wisconsin, USA.
Adam
A
Jochem
Genome Center of Wisconsin, Madison, Wisconsin, USA.|Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Matthew J P
MJP
Rush
Genome Center of Wisconsin, Madison, Wisconsin, USA.|Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Arne
A
Ulbrich
Morgridge Institute for Research, Madison, Wisconsin, USA.|Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Kyle P
KP
Robinson
Genome Center of Wisconsin, Madison, Wisconsin, USA.|Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Paul D
PD
Hutchins
Morgridge Institute for Research, Madison, Wisconsin, USA.|Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Mike T
MT
Veling
Morgridge Institute for Research, Madison, Wisconsin, USA.|Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Xiao
X
Guo
Morgridge Institute for Research, Madison, Wisconsin, USA.|Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Zachary A
ZA
Kemmerer
Genome Center of Wisconsin, Madison, Wisconsin, USA.|Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Kyle J
KJ
Connors
Genome Center of Wisconsin, Madison, Wisconsin, USA.|Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Edna A
EA
Trujillo
Morgridge Institute for Research, Madison, Wisconsin, USA.|Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Jacob
J
Sokol
Genome Center of Wisconsin, Madison, Wisconsin, USA.
Harald
H
Marx
Genome Center of Wisconsin, Madison, Wisconsin, USA.
Michael S
MS
Westphall
Genome Center of Wisconsin, Madison, Wisconsin, USA.
Alexander S
AS
Hebert
Morgridge Institute for Research, Madison, Wisconsin, USA.|Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
David J
DJ
Pagliarini
Genome Center of Wisconsin, Madison, Wisconsin, USA.|Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.|Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Joshua J
JJ
Coon
D002478:Cells, Cultured; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry; D055442:Metabolome / Q000502:physiology; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010449:Peptide Mapping; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D024101:Mitochondrial Proteins; D020543:Proteome
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