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MitoMiner, an integrated database for the storage and analysis of mitochondrial proteomics data.

Smith AC, Robinson AJ - Mol. Cell Proteomics (2009)

Bottom Line: Many experiments have attempted to define the mitochondrial proteome, resulting in large and complex data sets that are difficult to analyze.To address this, we developed a new public resource for the storage and investigation of this mitochondrial proteomics data, called MitoMiner, that uses a model to describe the proteomics data and associated biological information.Furthermore analysis indicated that enzymes of some cytosolic metabolic pathways are regularly detected in mitochondrial proteomics experiments, suggesting that they are associated with the outside of the outer mitochondrial membrane.

View Article: PubMed Central - PubMed

Affiliation: MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB20XY, United Kingdom.

ABSTRACT
Mitochondria are a vital component of eukaryotic cells with functions that extend beyond energy production to include metabolism, signaling, cell growth, and apoptosis. Their dysfunction is implicated in a large number of metabolic, degenerative, and age-related human diseases. Therefore, it is important to characterize and understand the mitochondrion. Many experiments have attempted to define the mitochondrial proteome, resulting in large and complex data sets that are difficult to analyze. To address this, we developed a new public resource for the storage and investigation of this mitochondrial proteomics data, called MitoMiner, that uses a model to describe the proteomics data and associated biological information. The proteomics data of 33 publications from both mass spectrometry and green fluorescent protein tagging experiments were imported and integrated with protein annotation from UniProt and genome projects, metabolic pathway data from Kyoto Encyclopedia of Genes and Genomes, homology relationships from HomoloGene, and disease information from Online Mendelian Inheritance in Man. We demonstrate the strengths of MitoMiner by investigating these data sets and show that the number of different mitochondrial proteins that have been reported is about 3700, although the number of proteins common to both animals and yeast is about 1400, and membrane proteins appear to be underrepresented. Furthermore analysis indicated that enzymes of some cytosolic metabolic pathways are regularly detected in mitochondrial proteomics experiments, suggesting that they are associated with the outside of the outer mitochondrial membrane. The data and advanced capabilities of MitoMiner provide a framework for further mitochondrial analysis and future systems level modeling of mitochondrial physiology.

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The numbers of orthologous proteins among three mitochondrial proteomes. A protein was assigned as mitochondrial by either experimental evidence (mass spectrometry or GFP tagging) or annotation or by the mitochondrial localization of an ortholog. Main numbers were calculated by using HomoloGene to determine redundancy and orthology among proteins. Numbers in parentheses were calculated by using BLAST (with a threshold of 10−35 for the expect score) to define orthologs.
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f9: The numbers of orthologous proteins among three mitochondrial proteomes. A protein was assigned as mitochondrial by either experimental evidence (mass spectrometry or GFP tagging) or annotation or by the mitochondrial localization of an ortholog. Main numbers were calculated by using HomoloGene to determine redundancy and orthology among proteins. Numbers in parentheses were calculated by using BLAST (with a threshold of 10−35 for the expect score) to define orthologs.

Mentions: To determine the mitochondrial proteins that were common among H. sapiens, M. musculus, and S. cerevisiae, we assessed the overlap in the mitochondrial proteomes we had calculated. Many of the proposed mitochondrial proteins of H. sapiens, M. musculus, and S. cerevisiae were orthologous using the relationships defined in HomoloGene (Fig. 9). Over 90% of the mitochondrial proteins from H. sapiens and M. musculus were orthologous, whereas about 50% of the proteins of S. cerevisiae were orthologous to proteins of H. sapiens and M. musculus. However, among the proteins that were considered to be non-orthologous between H. sapiens and M. musculus according to HomoloGene, there were examples of known orthologs. Therefore, more distant orthologies than defined by HomoloGene were identified by comparing all the proteins using BLASTP with an expect value cutoff of 10−35. Subsequently the number of proteins unique to S. cerevisiae fell to 562, whereas the number of orthologs present in all three species rose to 1393, and those in both H. sapiens and M. musculus rose to 3330 (close to 99% of the reported proteins). Of the remaining species-specific proteins in H. sapiens and M. musculus, several had an expect value slightly greater than that used for the BLASTP cutoff, and a couple had orthologs in RefSeq, but these sequences were missing from UniProt. The remaining singletons were all small proteins under 100 amino acids in length, and some were annotated as hypothetical.


MitoMiner, an integrated database for the storage and analysis of mitochondrial proteomics data.

Smith AC, Robinson AJ - Mol. Cell Proteomics (2009)

The numbers of orthologous proteins among three mitochondrial proteomes. A protein was assigned as mitochondrial by either experimental evidence (mass spectrometry or GFP tagging) or annotation or by the mitochondrial localization of an ortholog. Main numbers were calculated by using HomoloGene to determine redundancy and orthology among proteins. Numbers in parentheses were calculated by using BLAST (with a threshold of 10−35 for the expect score) to define orthologs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2690483&req=5

f9: The numbers of orthologous proteins among three mitochondrial proteomes. A protein was assigned as mitochondrial by either experimental evidence (mass spectrometry or GFP tagging) or annotation or by the mitochondrial localization of an ortholog. Main numbers were calculated by using HomoloGene to determine redundancy and orthology among proteins. Numbers in parentheses were calculated by using BLAST (with a threshold of 10−35 for the expect score) to define orthologs.
Mentions: To determine the mitochondrial proteins that were common among H. sapiens, M. musculus, and S. cerevisiae, we assessed the overlap in the mitochondrial proteomes we had calculated. Many of the proposed mitochondrial proteins of H. sapiens, M. musculus, and S. cerevisiae were orthologous using the relationships defined in HomoloGene (Fig. 9). Over 90% of the mitochondrial proteins from H. sapiens and M. musculus were orthologous, whereas about 50% of the proteins of S. cerevisiae were orthologous to proteins of H. sapiens and M. musculus. However, among the proteins that were considered to be non-orthologous between H. sapiens and M. musculus according to HomoloGene, there were examples of known orthologs. Therefore, more distant orthologies than defined by HomoloGene were identified by comparing all the proteins using BLASTP with an expect value cutoff of 10−35. Subsequently the number of proteins unique to S. cerevisiae fell to 562, whereas the number of orthologs present in all three species rose to 1393, and those in both H. sapiens and M. musculus rose to 3330 (close to 99% of the reported proteins). Of the remaining species-specific proteins in H. sapiens and M. musculus, several had an expect value slightly greater than that used for the BLASTP cutoff, and a couple had orthologs in RefSeq, but these sequences were missing from UniProt. The remaining singletons were all small proteins under 100 amino acids in length, and some were annotated as hypothetical.

Bottom Line: Many experiments have attempted to define the mitochondrial proteome, resulting in large and complex data sets that are difficult to analyze.To address this, we developed a new public resource for the storage and investigation of this mitochondrial proteomics data, called MitoMiner, that uses a model to describe the proteomics data and associated biological information.Furthermore analysis indicated that enzymes of some cytosolic metabolic pathways are regularly detected in mitochondrial proteomics experiments, suggesting that they are associated with the outside of the outer mitochondrial membrane.

View Article: PubMed Central - PubMed

Affiliation: MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB20XY, United Kingdom.

ABSTRACT
Mitochondria are a vital component of eukaryotic cells with functions that extend beyond energy production to include metabolism, signaling, cell growth, and apoptosis. Their dysfunction is implicated in a large number of metabolic, degenerative, and age-related human diseases. Therefore, it is important to characterize and understand the mitochondrion. Many experiments have attempted to define the mitochondrial proteome, resulting in large and complex data sets that are difficult to analyze. To address this, we developed a new public resource for the storage and investigation of this mitochondrial proteomics data, called MitoMiner, that uses a model to describe the proteomics data and associated biological information. The proteomics data of 33 publications from both mass spectrometry and green fluorescent protein tagging experiments were imported and integrated with protein annotation from UniProt and genome projects, metabolic pathway data from Kyoto Encyclopedia of Genes and Genomes, homology relationships from HomoloGene, and disease information from Online Mendelian Inheritance in Man. We demonstrate the strengths of MitoMiner by investigating these data sets and show that the number of different mitochondrial proteins that have been reported is about 3700, although the number of proteins common to both animals and yeast is about 1400, and membrane proteins appear to be underrepresented. Furthermore analysis indicated that enzymes of some cytosolic metabolic pathways are regularly detected in mitochondrial proteomics experiments, suggesting that they are associated with the outside of the outer mitochondrial membrane. The data and advanced capabilities of MitoMiner provide a framework for further mitochondrial analysis and future systems level modeling of mitochondrial physiology.

Show MeSH