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

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

Effects of Foliar Nutrition on Onion Seed Storage under Modified Atmosphere Packages

Modified atmosphere packaging (MAP) and controlled atmosphere storage techniques to reduce the oxygen around the food arelargely used for the preservation of fresh produce. There have been great technological advances in this area of preservation, particularly asit refers to improving the quality and shelf-stability of highly perishable food products, such as produce. Two successive winter seasons of2008/2009 and 2009/2010 were conducted under sandy soil conditions to study the effect of spraying with 12 commercial compounds ononion seeds storage under modified atmosphere packages. Germination percent of seeds decreased in 5°C than storage in room temperature.Germination percent of seeds was gradually decreased with increasing the storage period. Packaging treatments had a significant effect ongermination percent of seeds. All the packaging treatments had the higher germination percent than the paper package (control). The highestgermination percent after 12 months of storage was recorded for the treatment with non perforated polypropylene in room temperatureand polyethylene and non perforated polypropylene in 5°C. Catalase activity decreased with the prolongation of storage period. The nonperforated polypropylene package had the highest catalase activity. The treatment with non perforated polypropylene had the highest catalaseactivity after 12 months of storage in both room and 5°C temperatures. Peroxidase activity of seeds was gradually decreased with increasingthe storage period. The highest peroxidase activity after 12 months of storage was recorded in non perforated polypropylene in both storagetemperatures