Abstract
Mitochondrion plays a central role in diverse biological processes in most eukaryotes, and its dysfunctions are critically involved in a large number of diseases and the aging process. A systematic identification of mitochondrial proteomes and characterization of functional linkages among mitochondrial proteins are fundamental in understanding the mechanisms underlying biological functions and human diseases associated with mitochondria. Here we present a database MitProNet which provides a comprehensive knowledgebase for mitochondrial proteome, interactome and human diseases. First an inventory of mammalian mitochondrial proteins was compiled by widely collecting proteomic datasets, and the proteins were classified by machine learning to achieve a high-confidence list of mitochondrial proteins. The current version of MitProNet covers 1124 high-confidence proteins, and the remainders were further classified as middle- or low-confidence. An organelle-specific network of functional linkages among mitochondrial proteins was then generated by integrating genomic features encoded by a wide range of datasets including genomic context, gene expression profiles, protein-protein interactions, functional similarity and metabolic pathways. The functional-linkage network should be a valuable resource for the study of biological functions of mitochondrial proteins and human mitochondrial diseases. Furthermore, we utilized the network to predict candidate genes for mitochondrial diseases using prioritization algorithms. All proteins, functional linkages and disease candidate genes in MitProNet were annotated according to the information collected from their original sources including GO, GEO, OMIM, KEGG, MIPS, HPRD and so on. MitProNet features a user-friendly graphic visualization interface to present functional analysis of linkage networks. As an up-to-date database and analysis platform, MitProNet should be particularly helpful in comprehensive studies of complicated biological mechanisms underlying mitochondrial functions and human mitochondrial diseases. MitProNet is freely accessible at http://bio.scu.edu.cn:8085/MitProNet.
Highlights
Almost all eukaryotic organisms possess mitochondria as their essential cellular components that function as the center of energy production, metabolism, signaling, apoptosis and cell growth [1]
An inventory of mammalian mitochondrial proteins Pagliarini et al presented the most comprehensive mammalian mitochondrial proteome with nearly 1100 proteins and estimated that their compendium covers more than 85% of the mitochondrial proteome [14], Meisinger et al speculated that they may underestimate the size of the mammalian mitochondrial proteome and that the total number of mammalian genes for mitochondrial proteins could approach 1500 [28]
Considering the limitation of the databases, as a first step, we needed to compile an inventory of mammalian mitochondrial proteins that covers as many proteins as possible in the organelle
Summary
Almost all eukaryotic organisms possess mitochondria as their essential cellular components that function as the center of energy production, metabolism, signaling, apoptosis and cell growth [1]. Mitochondrial dysfunctions are known to be associated with a broad spectrum of metabolic and age-related diseases in humans, including diabetes mellitus, several cancer types, cardiovascular disorders, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease [2,3,4,5,6]. Since these mitochondria-related diseases are caused by multigenic factors and have complex clinical phenotypes, they still remain to be poorly understood and difficult to develop medical therapy. Some performed the bioinformatics methods to improve the confidence and the coverage of mitochondrial proteomes [14]
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