Mitochondrial protein functions elucidated by multi-omic mass spectrometry profiling
- Univ. of Wisconsin, Madison, WI (United States); Morgridge Inst. for Research, Madison, WI (United States); OSTI
- Univ. of Wisconsin, Madison, WI (United States); Genome Center of Wisconsin, Madison, WI (United States)
- Morgridge Inst. for Research, Madison, WI (United States)
- Univ. of Wisconsin, Madison, WI (United States); Morgridge Inst. for Research, Madison, WI (United States)
- Genome Center of Wisconsin, Madison, WI (United States)
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 broad molecular insights into mitochondrial protein functions.
- Research Organization:
- Univ. of Wisconsin, Madison, WI (United States)
- Sponsoring Organization:
- USDOE
- Grant/Contract Number:
- FC02-07ER64494
- OSTI ID:
- 1463133
- Journal Information:
- Nature Biotechnology, Journal Name: Nature Biotechnology Journal Issue: 11 Vol. 34; ISSN 1087-0156
- Publisher:
- Springer NatureCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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