MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins

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.

Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome

“…Mitochondrial proteins were defined through matching of gene names and Ensembl gene IDs to the Mitocarta2.0 dataset. 46 LFQ Intensity values were Log 2 transformed, and mean and standard deviations were calculated for each experimental group, consisting of either three control fibroblast biological replicates or two subject fibroblast technical replicates. Values from a group with a standard deviation > 0.3 were invalidated by conversion to ''NaN'' and rows were filtered to contain at least two valid values in both experimental groups.…”

The role of mitochondria in cardiac development and protection

“…As mentioned earlier, only 13 subunits of respiratory chain complexes are encoded by the mitochondrial DNA (mtDNA), whereas the over 1,000 nuclear encoded mitochondrial (NEM) proteins include the components of metabolic pathways, RC complexes, various assembly factors, carrier proteins as well as factors required for maintenance and expression of mtDNA [59].…”

Comparative Analysis of Mitochondrial N-Termini from Mouse, Human, and Yeast

“…At exactly pH 8.2, TMPP chemically modifies free N-termini but not lysine side chains, and then the N-termini are determined from peptides with TMPP doublets containing both C12 and C13. This study identified N-termini for 356 human genes, 179 of which are in the MitoCarta2.0 catalog of mitochondrial proteins (2), whereas the remainder may be co-purifying contaminants. These two high throughput studies of mitochondrial N-termini are extremely useful resources to understand individual mitochondrial proteins as well as protein import mechanisms.…”

“…A double membrane divides mitochondria into distinct compartments (matrix, inner membrane, intermembrane space, and outer membrane) that carry out specialized cellular processes, including oxidative phosphorylation, iron-sulfur cluster biogenesis, and a myriad biosynthetic pathways. Mammalian mitochondria contain a tiny genome encoding 13 proteins, whereas the remaining ϳ1200 proteins (1,2) are encoded in the nucleus and imported into the organelle. Although there are several different mechanisms that can target proteins to the mitochondrion, the predominant mechanism is via an N-terminal presequence that directs import through the double membrane, which is subsequently cleaved to produce the mature, functional protein (3).…”