Mitochondrial protein functions elucidated by multi-omic mass spectrometry profiling

作者：Stefely Jonathan A; Kwiecien Nicholas W; Freiberger Elyse C; Richards Alicia L; Jochem Adam; Rush Matthew J P; Ulbrich Arne; Robinson Kyle P; Hutchins Paul D; Veling Mike T; Guo Xiao; Kemmerer Zachary A; Connors Kyle J; Trujillo Edna A; Sokol Jacob; Marx Harald; Westphall Michael S; Hebert Alexander S; Pagliarini David J; Coon Joshua J

来源：Nature Biotechnology, 2016, 34(11): 1191-+.

DOI：10.1038/nbt.3683

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.

• 出版日期2016-11