Abstract
Mitochondria are complex organelles that house essential pathways involved in energy metabolism, ion homeostasis, signalling and apoptosis. To understand mitochondrial pathways in health and disease, it is crucial to have an accurate inventory of the organelle's protein components. In 2008, we made substantial progress toward this goal by performing in-depth mass spectrometry of mitochondria from 14 organs, epitope tagging/microscopy and Bayesian integration to assemble MitoCarta (www.broadinstitute.org/pubs/MitoCarta): an inventory of genes encoding mitochondrial-localized proteins and their expression across 14 mouse tissues. Using the same strategy we have now reconstructed this inventory separately for human and for mouse based on (i) improved gene transcript models, (ii) updated literature curation, including results from proteomic analyses of mitochondrial sub-compartments, (iii) improved homology mapping and (iv) updated versions of all seven original data sets. The updated human MitoCarta2.0 consists of 1158 human genes, including 918 genes in the original inventory as well as 240 additional genes. The updated mouse MitoCarta2.0 consists of 1158 genes, including 967 genes in the original inventory plus 191 additional genes. The improved MitoCarta 2.0 inventory provides a molecular framework for system-level analysis of mammalian mitochondria.
Highlights
There is increasing appreciation for the essential roles that mitochondria play in oxidative phosphorylation and energy metabolism, and in small molecule metabolism, ion homeostasis, immune signalling and cell death
Using a naıve Bayes integration [5], every mouse gene was assigned a combined score of mitochondrial localization from the seven data sources, each weighted by its accuracy based on large training sets of known mitochondrial and non-mitochondrial mouse genes
The resulting MitoCarta1.0 inventory of 1098 mouse genes contained 591 curated mitochondrial components used for training, 131 proteins validated using GFP/microscopy, and 376 proteins assigned to the organelle at a 10% false discovery rate (FDR)
Summary
There is increasing appreciation for the essential roles that mitochondria play in oxidative phosphorylation and energy metabolism, and in small molecule metabolism, ion homeostasis, immune signalling and cell death. Mitochondria originally descended from an endosymbiotic bacterium, predicted to resemble modern-day ␣-proteobacteria, early in eukaryotic evolution [1]. Mammalian mitochondria contain their own genome (mtDNA), which encodes a total of 13 proteins that are all core components of oxidative phosphorylation. In 2008, we constructed the MitoCarta1.0 inventory of mitochondrial proteins using multiple experimental and computational approaches [4]. The resulting MitoCarta1.0 inventory of 1098 mouse genes contained 591 curated mitochondrial components used for training, 131 proteins validated using GFP/microscopy, and 376 proteins assigned to the organelle at a 10% false discovery rate (FDR).
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