Integrative analysis of the mitochondrial proteome in yeast.

Integrative analysis of the mitochondrial proteome in yeast.
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DOI:
10.1371/journal.pbio.0020160
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发表时间:
2004-06
期刊:
影响因子:
9.8
通讯作者:
Steinmetz LM
Steinmetz LM
中科院分区:
生物学1区
文献类型:
--
作者:
Prokisch H;Scharfe C;Camp DG 2nd;Xiao W;David L;Andreoli C;Monroe ME;Moore RJ;Gritsenko MA;Kozany C;Hixson KK;Mottaz HM;Zischka H;Ueffing M;Herman ZS;Davis RW;Meitinger T;Oefner PJ;Smith RD;Steinmetz LM

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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. Although individual approaches fall short, integrating multiple common genetic and biochemical approaches yields a description of mitochondrial proteins that is more than the sum of its parts
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