Database Commons

a catalog of worldwide biological databases

Defining the mitochondrial proteome is a prerequisite for fully understanding the organelles function as well as mechanisms underlying mitochondrial pathology. The core functions of mitochondria include oxidative phosphorylation, amino acid metabolism, fatty acid oxidation, and ion homeostasis. In addition to these well-known functions, many crucial properties in cell signaling, cell differentiation and cell death are only now being elucidated, and with them the proteins involved. With the wealth of information arriving from single protein studies and sophisticated genome-wide approaches, MitoP2 was designed and is maintained to consolidate knowledge on mitochondrial proteins in one comprehensive database, thus making all pertinent data readily accessible (http://www.mitop2.de). Although the identification of the human mitochondrial proteome is ultimately the prime objective, integration of other species includes Saccharomyces cerevisiae, mouse, Arabidopsis thaliana, and Neurospora crassa so orthology between these species can be interrogated. Data from genome-wide studies can be individually retrieved and are also processed by a support vector machine (SVM) to generate a score that indicates the likelihood of a candidate protein having a mitochondrial location. Manually validated proteins constitute the reference set of the database that contains over 590 yeast, 920 human, and 1020 mouse entries, and that is used for benchmarking the SVM score. Multiple search options allow for the interrogation of the reference set, candidates, disease related proteins, chromosome locations as well as availability of mouse models. Taken together, MitoP2 is a valuable tool for basic scientists, geneticists, and clinicians who are investigating mitochondrial physiology and dysfunction.

The impact of mitochondria on several fundamental cellular processes is reflected in their involvement in the pathophysiology of common diseases such as Parkinson's disease, diabetes, and obesity and a wide range of monogenic disorders primarily associated with energy impairment or metabolic diseases. The importance of mitochondria is also reflected by the steep increase of proteins, which has been localized to this organelle. In yeast, more than 500 of the expected 700-800 mitochondrial proteins are already annotated. In the mammalian species, the expected numbers are estimated to be in the range of 1500-2000 proteins, and the currently annotated entries reach almost 700. In addition to the studies dealing with single proteins, there are many high-throughput approaches that improve the description of the mitochondrial proteome. They include computational predictions of signaling sequences, proteome mapping, mutant screening, expression profiling, protein-protein interaction, and cellular sublocalization studies. The MitoP2 database (http://www.mitop2.de/) was established to structure, explore, and customize the available data on mitochondrial proteins, functions, and diseases. MitoP2 provides a comprehensive picture of the mitochondrial proteome by focusing on (1) the orthology between species, including Saccharomyces cerevisiae, mouse, humans, and Arabidopsis thaliana; (2) the definition of mitochondrial reference sets in these species; (3) the integration of data predictive for mitochondrial localization or function stemming from genomewide approaches; (4) the allocation of a gateway for functional data from model systems and genetics of mitochondriopathies; and (5) the calculation of a combined score for each protein summarizing the indirect evidence for a mitochondrial localization. All data are accessible via search tools and linked to the original data source. By providing an overview of functional annotations from different databases, the MitoP2 database lends itself to genetic investigations of human mitochondriopathies.

The aim of the MitoP2 database (http://ihg.gsf.de/mitop2) is to provide a comprehensive list of mitochondrial proteins of yeast and man. Based on the current literature we created an annotated reference set of yeast and human proteins. In addition, data sets relevant to the study of the mitochondrial proteome are integrated and accessible via search tools and links. They include computational predictions of signalling sequences, and summarize results from proteome mapping, mutant screening, expression profiling, protein-protein interaction and cellular sublocalization studies. For each individual approach, specificity and sensitivity for allocating mitochondrial proteins was calculated. By providing the evidence for mitochondrial candidate proteins the MitoP2 database lends itself to the genetic characterization of human mitochondriopathies.

The MITOP database http://websvr.mips.biochem.mpg. de/proj/medgen/mitop/ consolidates information on both nuclear- and mitochondrial-encoded genes and their proteins. The five species files- Saccharomyces cerevisiae, Mus musculus, Caenorhabditis elegans, Neurospora crassa and Homo sapiens -include annotated data derived from a variety of online resources and the literature. A wide spectrum of search facilities is given in the interelated sections 'Gene catalogues', 'Protein catalogues', 'Homologies', 'Pathways and metabolism', and 'Human disease catalogue' including extensive references and hyperlinks for each entry. Precomputed FASTA searches using all the MITOP yeast protein entries and a list of the best EST hits with graphical cluster alignments related to the yeast reference sequence are presented. The MITOP orthologue tables with cross-listing to all the protein entries for each species in the database facilitate investigations into interspecies homology. A program (MITOPROT) is available to identify mitochondrial targeting sequences and graphical depictions of several important mitochondrial processes are included. The 'Human disease catalogue' lists a total of 101 disorders related to mitochondrial protein abnormalities, sorted by clinical criteria and age of onset.