MitoMiner: a data warehouse for mitochondrial proteomics data

Smith, Anthony C.; Blackshaw, James; Robinson, Alan J.

doi:10.1093/nar/gkr1101

Cited by 90 publications

(82 citation statements)

References 31 publications

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“…Similarly, only 2 of the 51 nuencoded mitochondrial membrane proteins with known structures were classified as arrested by SRP (SI Appendix, Table S2). Consistent with these results, 251 of 281 nu-encoded membrane proteins localized to mitochondria with the aid of green fluorescent protein tags in yeast and humans (29) were predicted to avoid recognition by SRP (SI Appendix, Fig. S1 and Table S3).…”

Section: Mitochondrial Proteins Are Potential Targets For Recognitionsupporting

confidence: 62%

Mitochondrial genomes are retained by selective constraints on protein targeting

Björkholm

Harish

Hagström

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Mitochondria are energy-producing organelles in eukaryotic cells considered to be of bacterial origin. The mitochondrial genome has evolved under selection for minimization of gene content, yet it is not known why not all mitochondrial genes have been transferred to the nuclear genome. Here, we predict that hydrophobic membrane proteins encoded by the mitochondrial genomes would be recognized by the signal recognition particle and targeted to the endoplasmic reticulum if they were nuclear-encoded and translated in the cytoplasm. Expression of the mitochondrially encoded proteins Cytochrome oxidase subunit 1, Apocytochrome b, and ATP synthase subunit 6 in the cytoplasm of HeLa cells confirms export to the endoplasmic reticulum. To examine the extent to which the mitochondrial proteome is driven by selective constraints within the eukaryotic cell, we investigated the occurrence of mitochondrial protein domains in bacteria and eukaryotes. The accessory protein domains of the oxidative phosphorylation system are unique to mitochondria, indicating the evolution of new protein folds. Most of the identified domains in the accessory proteins of the ribosome are also found in eukaryotic proteins of other functions and locations. Overall, one-third of the protein domains identified in mitochondrial proteins are only rarely found in bacteria. We conclude that the mitochondrial genome has been maintained to ensure the correct localization of highly hydrophobic membrane proteins. Taken together, the results suggest that selective constraints on the eukaryotic cell have played a major role in modulating the evolution of the mitochondrial genome and proteome. mitochondria | protein domain | evolution | endoplasmatic reticulum | signal recognition particle

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Section: Mitochondrial Proteins Are Potential Targets For Recognitionsupporting

confidence: 62%

Mitochondrial genomes are retained by selective constraints on protein targeting

Björkholm

Harish

Hagström

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…COMPLEAT (12) was used to identify complexes enriched among the genes identified by APEX. To build MitoMax, a comprehensive database for Drosophila mitochondrial genes with subcompartmental annotation, genes identified from isolation-based studies and/or APEX labeling were combined and integrated with genes from annotation as well as Drosophila genes annotated at MitoMiner (18) and MitoDrome (19).…”

Section: Methodsmentioning

confidence: 99%

“…To build a comprehensive database, MitoMax, for Drosophila mitochondrial proteins with subcompartmental annotation, Drosophila genes identified by either isolation-based studies (16,17) or by our APEX labeling approach were combined and integrated with genes from human annotation (1,290 genes) as well as Drosophila genes annotated at MitoMiner (18) and MitoDrome (19) (Fig. S8; genepath.med.…”

Section: The Mitomax Database For Drosophila Mitochondrial Genes Withmentioning

confidence: 99%

Proteomic mapping in live Drosophila tissues using an engineered ascorbate peroxidase

Chen

Udeshi

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

143

147

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Characterization of the proteome of organelles and subcellular domains is essential for understanding cellular organization and identifying protein complexes as well as networks of protein interactions. We established a proteomic mapping platform in live Drosophila tissues using an engineered ascorbate peroxidase (APEX). Upon activation, the APEX enzyme catalyzes the biotinylation of neighboring endogenous proteins that can then be isolated and identified by mass spectrometry. We demonstrate that APEX labeling functions effectively in multiple fly tissues for different subcellular compartments and maps the mitochondrial matrix proteome of Drosophila muscle to demonstrate the power of APEX for characterizing subcellular proteomes in live cells. Further, we generate “MitoMax,” a database that provides an inventory of Drosophila mitochondrial proteins with subcompartmental annotation. Altogether, APEX labeling in live Drosophila tissues provides an opportunity to characterize the organelle proteome of specific cell types in different physiological conditions.

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“…Each BN-PAGE gel was divided into 18 horizontal slices starting at 20 kDa, cut into 3-mm slices, increasing in molecular mass until reaching 1200 kDa, and subjected to in-gel digestion and mass spectrometry, as previously described [7]. Samples identified via mass spectrometry were run through the MitoMiner mitochondrial protein database to identify mitochondrial pathways [17] Normalization of MS data was corrected by calculating the slope of the averaged control versus treated hits, linearity was corrected by multiplying the control hits by 1.32, and the final quantification of total hits was plotted using Excel.…”

Section: In-gel Digestion and Mass Spectrometrymentioning

confidence: 99%

“…The mitochondria were isolated from the basal and stimulated cells, and the mitochondrial proteins were separated by BN-PAGE followed by mass spectrometry. We used MitoMiner, an integrated database for the analysis of mitochondrial proteins [17], to identify the proteins involved in specific mitochondrial pathways identified via the Kyoto Encyclopedia of Genes and Genomes with the number of hits in each gel slice charted (Supplemental Fig. S1, available online at www.biolreprod.org).…”

Section: Identification Of Protein Complexes In the Mitochondria Usinmentioning

confidence: 99%

Steroidogenesis in MA-10 Mouse Leydig Cells Is Altered via Fatty Acid Import into the Mitochondria1

Rone

Midzak

Martinez–Arguelles

et al. 2014

Biology of Reproduction

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Mitochondria are home to many cellular processes, including oxidative phosphorylation and fatty acid metabolism, and in steroid-synthesizing cells, they are involved in cholesterol import and metabolism, which is the initiating step in steroidogenesis. The formation of macromolecular protein complexes aids in the regulation and efficiency of these mitochondrial functions, though because of their dynamic nature, they are hard to identify. To overcome this problem, we used Blue-Native PAGE with whole-gel mass spectrometry on isolated mitochondria from control and hormone-treated MA-10 mouse tumor Leydig cells. The presence of multiple mitochondrial protein complexes was shown. Although these were qualitatively similar under control and human chorionic gonadotropin (hCG)-stimulated conditions, quantitative differences in the components of the complexes emerged after hCG treatment. A prominent decrease was observed with proteins involved in fatty acid import into the mitochondria, implying that mitochondrial beta-oxidation is not essential for steroidogenesis. To confirm this observation, we inhibited fatty acid import utilizing the CPT1a inhibitor etomoxir, resulting in increased steroid production. Conversely, stimulation of mitochondrial beta-oxidation with metformin resulted in a dose-dependent reduction in steroidogenesis. These changes were accompanied by changes in mitochondrial respiration and in the lactic acid formed during glycolysis. Taken together, these results suggest that upon hormonal stimulation, mitochondria efficiently import cholesterol for steroid production at the expense of other lipids necessary for energy production, specifically fatty acids required for beta-oxidation.

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MitoMiner: a data warehouse for mitochondrial proteomics data

Cited by 90 publications

References 31 publications

Mitochondrial genomes are retained by selective constraints on protein targeting

Mitochondrial genomes are retained by selective constraints on protein targeting

Proteomic mapping in live Drosophila tissues using an engineered ascorbate peroxidase

Steroidogenesis in MA-10 Mouse Leydig Cells Is Altered via Fatty Acid Import into the Mitochondria1

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