Open AccessMitochondrial protein functions elucidated by multi-omic mass spectrometry profiling
Author(s) -
Jonathan A. Stefely,
Nicholas W. Kwiecien,
Elyse C. Freiberger,
Alicia Richards,
Adam Jochem,
Matthew J. P. Rush,
Arne Ulbrich,
Kyle Robinson,
Paul D. Hutchins,
Mike T. Veling,
Xiao Guo,
Zachary A. Kemmerer,
Kyle J Connors,
Edna A. Trujillo,
Jacob Sokol,
Harald Marx,
Michael S. Westphall,
Alexander S. Hebert,
David J. Pagliarini,
Joshua J. Coon
Publication year - 2016
Publication title -
nature biotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.358
H-Index - 445
eISSN - 1546-1696
pISSN - 1087-0156
DOI - 10.1038/nbt.3683
Subject(s) - biology , proteomics , proteome , mitochondrion , computational biology , mitochondrial disease , neurodegeneration , gene , biochemistry , mitochondrial dna , disease , medicine , pathology
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.