MitoP2: the mitochondrial proteome database—now including mouse data

The MitoP2 database () integrates information on mitochondrial proteins, their molecular functions and associated diseases. The central database features are manually annotated reference proteins localized or functionally associated with mitochondria supplied for yeast, human and mouse. MitoP2 enables (i) the identification of putative orthologous proteins between these species to study evolutionarily conserved functions and pathways; (ii) the integration of data from systematic genome-wide studies such as proteomics and deletion phenotype screening; (iii) the prediction of novel mitochondrial proteins using data integration and the assignment of evidence scores; and (iv) systematic searches that aim to find the genes that underlie common and rare mitochondrial diseases. The data and analysis files are referenced to data sources in PubMed and other online databases and can be easily downloaded. MitoP2 users can explore the relationship between mitochondrial dysfunctions and disease and utilize this information to conduct systems biology approaches on mitochondria

A mutation screening of oncogenes, tumor suppressor gene TP53 and nuclear encoded mitochondrial complex I genes in oncocytic thyroid tumors.

Background: Thyroid neoplasias with oncocytic features represent a specific phenotype in non-medullary thyroid cancer, reflecting the unique biological phenomenon of mitochondrial hyperplasia in the cytoplasm. Oncocytic thyroid cells are characterized by a prominent eosinophilia (or oxyphilia) caused by mitochondrial abundance. Although disruptive mutations in the mitochondrial DNA (mtDNA) are the most significant hallmark of such tumors, oncocytomas may be envisioned as heterogeneous neoplasms, characterized by multiple nuclear and mitochondrial gene lesions. We investigated the nuclear mutational profile of oncocytic tumors to pinpoint the mutations that may trigger the early oncogenic hit. Methods: Total DNA was extracted from paraffin-embedded tissues from 45 biopsies of oncocytic tumors. High-resolution melting was used for mutation screening of mitochondrial complex I subunits genes. Specific nuclear rearrangements were investigated by RT-PCR (RET/PTC) or on isolated nuclei by interphase FISH (PAX8/PPARγ). Recurrent point mutations were analyzed by direct sequencing. Results: In our oncocytic tumor samples, we identified rare TP53 mutations. The series of analyzed cases did not include poorly- or undifferentiated thyroid carcinomas, and none of the TP53 mutated cases had significant mitotic activity or high-grade features. Thus, the presence of disruptive TP53 mutations was completely unexpected. In addition, novel mutations in nuclear-encoded complex I genes were identified. Conclusions: These findings suggest that nuclear genetic lesions altering the bioenergetics competence of thyroid cells may give rise to an aberrant mitochondria-centered compensatory mechanism and ultimately to the oncocytic phenotype. Keywords: Oncocytic carcinoma, Nuclear mitochondrial complex I subunits, Oncogene mutation analysi

Mapping gene associations in human mitochondria using clinical disease phenotypes

Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects within the mitochondrial system. The accompanying knowledgebase (http://www.mitophenome.org/) supports the study of clinical diseases and associated genes

InterMitoBase: An annotated database and analysis platform of protein-protein interactions for human mitochondria

<p>Abstract</p> <p>Background</p> <p>The mitochondrion is an essential organelle which plays important roles in diverse biological processes, such as metabolism, apoptosis, signal transduction and cell cycle. Characterizing protein-protein interactions (PPIs) that execute mitochondrial functions is fundamental in understanding the mechanisms underlying biological functions and diseases associated with mitochondria. Investigations examining mitochondria are expanding to the system level because of the accumulation of mitochondrial proteomes and human interactome. Consequently, the development of a database that provides the entire protein interaction map of the human mitochondrion is urgently required.</p> <p>Results</p> <p>InterMitoBase provides a comprehensive interactome of human mitochondria. It contains the PPIs in biological pathways mediated by mitochondrial proteins, the PPIs between mitochondrial proteins and non-mitochondrial proteins as well as the PPIs between mitochondrial proteins. The current version of InterMitoBase covers 5,883 non-redundant PPIs of 2,813 proteins integrated from a wide range of resources including PubMed, KEGG, BioGRID, HPRD, DIP and IntAct. Comprehensive curations have been made on the interactions derived from PubMed. All the interactions in InterMitoBase are annotated according to the information collected from their original sources, GenBank and GO. Additionally, InterMitoBase features a user-friendly graphic visualization platform to present functional and topological analysis of PPI networks identified. This should aid researchers in the study of underlying biological properties.</p> <p>Conclusions</p> <p>InterMitoBase is designed as an integrated PPI database which provides the most up-to-date PPI information for human mitochondria. It also works as a platform by integrating several on-line tools for the PPI analysis. As an analysis platform and as a PPI database, InterMitoBase will be an important database for the study of mitochondria biochemistry, and should be particularly helpful in comprehensive analyses of complex biological mechanisms underlying mitochondrial functions.</p

Ecotoxicology of Copper in Horticultural Soils: A Review

Nowadays, the world is facing the problem of environmental pollution because of the increase of man’s needs requires developmentin life activities, progress industrialization, transportation tools, enhancement of agriculture and exploitation of natural resources. Soil andwater resources are extremely exposed to pollution from different aspects. Agrochemicals in particular, have created severe problems, sincethey release thousands of chemicals to the environment. Several studies on the effect of environmental pollutants on agroecosystem have beencarried out. On the other hand, the importance of trace elements as environmental pollutants is well known and well documented in literature.Cu contamination to agricultural soils has been accelerated due to its wide and repeated use in agriculture and horticulture as fertilizers orfungicides to protect vines, citrus trees, and other fruit crops against fungus diseases. Applied Cu from different agrochemical sources to agroenvironment may be adsorbed and are transported to the groundwater table and pollute it besides polluting the soils. The use of Cu-basedfungicides in vineyard soils is widely documented worldwide. It has been found that many countries contain concentrations in excess of 100mg kg−1. Importance of study of transport of Cu arises due to the fact that Cu is absorbed in soils and also reaches the groundwater table,thus polluting both soil and ground water. It is often more important to be able to estimate the mobile fraction, the readily soluble fraction,the exchangeable fraction, or the plant available fraction of Cu content of a soil as a more direct indication of the likelihood of deleteriousor toxic effects on soils and groundwater. Therefore, the aim of present work was to highlight the behavior and ecotoxicological effects ofcopper on horticultural soils

Ecotoxicology of Copper in Horticultural Soils: A Review

Nowadays, the world is facing the problem of environmental pollution because of the increase of man’s needs requires development in life activities, progress industrialization, transportation tools, enhancement of agriculture and exploitation of natural resources. Soil and water resources are extremely exposed to pollution from different aspects. Agrochemicals in particular, have created severe problems, since they release thousands of chemicals to the environment. Several studies on the effect of environmental pollutants on agroecosystem have been carried out. On the other hand, the importance of trace elements as environmental pollutants is well known and well documented in literature. Cu contamination to agricultural soils has been accelerated due to its wide and repeated use in agriculture and horticulture as fertilizers or fungicides to protect vines, citrus trees, and other fruit crops against fungus diseases. Applied Cu from different agrochemical sources to agroenvironment may be adsorbed and are transported to the groundwater table and pollute it besides polluting the soils. The use of Cu-based fungicides in vineyard soils is widely documented worldwide. It has been found that many countries contain concentrations in excess of 100 mg kg−1. Importance of study of transport of Cu arises due to the fact that Cu is absorbed in soils and also reaches the groundwater table, thus polluting both soil and ground water. It is often more important to be able to estimate the mobile fraction, the readily soluble fraction, the exchangeable fraction, or the plant available fraction of Cu content of a soil as a more direct indication of the likelihood of deleterious or toxic effects on soils and groundwater. Therefore, the aim of present work was to highlight the behavior and ecotoxicological effects of copper on horticultural soils

Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia

Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates

Effect of Foliar Nutrition on Post-Harvest of Onion Seed under Sandy Soil and Saline Irrigation Water Conditions

Foliar application has been determined to be an effective nutrients delivery strategy in vegetable and fruits. The enhancement of vegetable and fruit yields affected by foliar nutrients application has been recognized in previously conducted studies with perennial tree crops. The efficiency of foliar nutrition is dependent on soil, climate, fertilizer and the amount of nitrogen used. There is no sufficient information concerning cooperation of foliar nutrition with all nutrients form as well as the rates of these nutrients fertilization in vegetableand fruit crops. Two successive winter seasons of 2008/2009 and 2009/2010 were conducted under sandy soil conditions to study the effect of spraying with 12 commercial compounds on inflorescences diameter, flower stalk length, number of seed stem /plant, weight of 1000 seed, germination percentage, seed yield, moisture content, catalase , peroxidase activity and malondialdehyde content of onion seeds. The plantssprayed with union Zn, union Mn, union feer, shams k, elga 600, boron, and amino x had the highest vegetative growth parameter, germination percent and enzyme activity. The plants sprayed with union Zn, union feer, shams K, magnesium, caboron, hummer and amino X had the highest seed yield ha-1. The seeds were stored for one year to study the effect of different commercial compounds and storage temperatures on germination, moisture content and change in antioxidant enzymes activities of onion seeds during the storage period. Storage at cold temperature showed higher germination percent, moisture content and lower malondialdehyde content than storage at room temperature. The treatment with union Zn, union feer, union Mn, boron, elga 600, caboron, amica, hummer and amino x had the highest germination percent

Effect of Foliar Nutrition on Post-Harvest of Onion Seed under Sandy Soil and Saline Irrigation Water Conditions

Foliar application has been determined to be an effective nutrients delivery strategy in vegetable and fruits. The enhancement of vegetable and fruit yields affected by foliar nutrients application has been recognized in previously conducted studies with perennial tree crops. The efficiency of foliar nutrition is dependent on soil, climate, fertilizer and the amount of nitrogen used. There is no sufficient information concerning cooperation of foliar nutrition with all nutrients form as well as the rates of these nutrients fertilization in vegetableand fruit crops. Two successive winter seasons of 2008/2009 and 2009/2010 were conducted under sandy soil conditions to study the effect of spraying with 12 commercial compounds on inflorescences diameter, flower stalk length, number of seed stem /plant, weight of 1000 seed, germination percentage, seed yield, moisture content, catalase , peroxidase activity and malondialdehyde content of onion seeds. The plantssprayed with union Zn, union Mn, union feer, shams k, elga 600, boron, and amino x had the highest vegetative growth parameter, germination percent and enzyme activity. The plants sprayed with union Zn, union feer, shams K, magnesium, caboron, hummer and amino X had the highest seed yield ha-1. The seeds were stored for one year to study the effect of different commercial compounds and storage temperatures on germination, moisture content and change in antioxidant enzymes activities of onion seeds during the storage period. Storage at cold temperature showed higher germination percent, moisture content and lower malondialdehyde content than storage at room temperature. The treatment with union Zn, union feer, union Mn, boron, elga 600, caboron, amica, hummer and amino x had the highest germination percent