Integrative Analysis of the Mitochondrial Proteome in Yeast
Open Access
- 15 June 2004
- journal article
- cell biology
- Published by Public Library of Science (PLoS) in PLoS Biology
- Vol. 2 (6), e160
- https://doi.org/10.1371/journal.pbio.0020160
Abstract
In this study yeast mitochondria were used as a model system to apply, evaluate, and integrate different genomic approaches to define the proteins of an organelle. Liquid chromatography mass spectrometry applied to purified mitochondria identified 546 proteins. By expression analysis and comparison to other proteome studies, we demonstrate that the proteomic approach identifies primarily highly abundant proteins. By expanding our evaluation to other types of genomic approaches, including systematic deletion phenotype screening, expression profiling, subcellular localization studies, protein interaction analyses, and computational predictions, we show that an integration of approaches moves beyond the limitations of any single approach. We report the success of each approach by benchmarking it against a reference set of known mitochondrial proteins, and predict approximately 700 proteins associated with the mitochondrial organelle from the integration of 22 datasets. We show that a combination of complementary approaches like deletion phenotype screening and mass spectrometry can identify over 75% of the known mitochondrial proteome. These findings have implications for choosing optimal genome-wide approaches for the study of other cellular systems, including organelles and pathways in various species. Furthermore, our systematic identification of genes involved in mitochondrial function and biogenesis in yeast expands the candidate genes available for mapping Mendelian and complex mitochondrial disorders in humans.Keywords
This publication has 41 references indexed in Scilit:
- Global analysis of protein localization in budding yeastNature, 2003
- 'Omics' of the mitochondrionNature Biotechnology, 2003
- Systematic screen for human disease genes in yeastNature Genetics, 2002
- Comparative assessment of large-scale data sets of protein–protein interactionsNature, 2002
- Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometryNature, 2002
- Functional organization of the yeast proteome by systematic analysis of protein complexesNature, 2002
- A comprehensive two-hybrid analysis to explore the yeast protein interactomeProceedings of the National Academy of Sciences of the United States of America, 2001
- A Bayesian system integrating expression data with sequence patterns for localizing proteins: comprehensive application to the yeast genomeJournal of Molecular Biology, 2000
- Gapped BLAST and PSI-BLAST: a new generation of protein database search programsNucleic Acids Research, 1997
- An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein databaseJournal of the American Society for Mass Spectrometry, 1994