MitoMiner v4.0: an updated database of mitochondrial localization evidence, phenotypes and diseases

Abstract

Increasing numbers of diseases are associated with mitochondrial dysfunction. This is unsurprising given mitochondria have major roles in bioenergy generation, signalling, detoxification, apoptosis and biosynthesis. However, fundamental questions of mitochondrial biology remain, including: which nuclear genes encode mitochondrial proteins; how their expression varies with tissue; and which are associated with disease. But experiments to catalogue the mitochondrial proteome are incomplete and sometimes contradictory. This arises because the mitochondrial proteome has tissue- and stage-specific variability, plus differences among experimental techniques and localization evidence types used. This leads to limitations in each technique's coverage and inevitably conflicting results. To support identification of mitochondrial proteins, we developed MitoMiner (http://mitominer.mrc-mbu.cam.ac.uk/), a database combining evidence of mitochondrial localization with information from public resources. Here we report upgrades to MitoMiner, including its re-engineering to be gene-centric to enable easier sharing of evidence among orthologues and support next generation sequencing, plus new data sources, including expression in different tissues, information on phenotypes and diseases of genetic mutations and a new mitochondrial proteome catalogue. MitoMiner is a powerful platform to investigate mitochondrial localization by providing a unique combination of experimental sub-cellular localization datasets, tissue expression, predictions of mitochondrial targeting sequences, gene annotation and links to phenotype and disease.

Figure 1.

Header of the MitoMiner gene entry for the human TIMM50 gene. MitoMiner's new gene-centric organization presents first an overview of primary mitochondrial localization evidence, then the gene’s homologues in other species and a table of their mitochondrial localization evidence, including experimental data, annotation and mutant phenotype. Links to this gene’s presence in catalogues of mitochondrial proteomes is provided, as well as links to external resources, e.g. OMIM and Ensembl. The remainder of the gene entry page (not shown) describes other information, including localization evidence, tissue expression data and links to metabolism.

Figure 2.

Mutant phenotype data for the mouse TIMM50 gene recorded in the phenotype section of its gene entry. Identifier names and descriptions are from the Mouse Genome Informatics (MGD) database. Cross-references between homologous genes means the existence of these mouse data are recorded in the ‘Homologue Phenotype Recorded?’ column in the summary table of the human TIMM50 gene entry (Figure 1).