keyword
https://read.qxmd.com/read/29694833/insights-into-the-role-of-the-peroxisomal-ubiquitination-machinery-in-pex13p-degradation-in-the-yeast-hansenula-polymorpha
#21
JOURNAL ARTICLE
Xin Chen, Srishti Devarajan, Natasha Danda, Chris Williams
The import of matrix proteins into peroxisomes in yeast requires the action of the ubiquitin-conjugating enzyme Pex4p and a complex consisting of the ubiquitin E3 ligases Pex2p, Pex10p and Pex12p. Together, this peroxisomal ubiquitination machinery is thought to ubiquitinate the cycling receptor protein Pex5p and members of the Pex20p family of co-receptors, a modification that is required for receptor recycling. However, recent reports have demonstrated that this machinery plays a role in additional peroxisome-associated processes...
May 25, 2018: Journal of Molecular Biology
https://read.qxmd.com/read/29458144/disruption-of-peroxisome-function-leads-to-metabolic-stress-mtor-inhibition-and-lethality-in-liver-cancer-cells
#22
JOURNAL ARTICLE
Mengjiao Cai, Xiao Sun, Wenchao Wang, Zhusheng Lian, Ping Wu, Suxia Han, Huan Chen, Pumin Zhang
Peroxisome houses a large number of enzymes involved in lipid and phytochemical oxidation as well as synthesis of bile acid and other specialized lipids. Peroxisome resident enzymes are imported into the organelle via a conserved cargo transport system composed of many peroxins, protein factors essential for the biogenesis of peroxisome. Among the peroxins, PEX5 plays a transporter role, and PEX2, 10, and 12 are thought to form a complex that functions as an E3 ubiquitin ligase to help recycle PEX5 in an ubiquitin modification-dependent process...
May 1, 2018: Cancer Letters
https://read.qxmd.com/read/29037759/a-new-yeast-peroxin-pex36-a-functional-homolog-of-mammalian-pex16-functions-in-the-er-to-peroxisome-traffic-of-peroxisomal-membrane-proteins
#23
COMPARATIVE STUDY
Jean-Claude Farré, Krypton Carolino, Oleh V Stasyk, Olena G Stasyk, Zlatan Hodzic, Gaurav Agrawal, Andreas Till, Marco Proietto, James Cregg, Andriy A Sibirny, Suresh Subramani
Peroxisomal membrane proteins (PMPs) traffic to peroxisomes by two mechanisms: direct insertion from the cytosol into the peroxisomal membrane and indirect trafficking to peroxisomes via the endoplasmic reticulum (ER). In mammals and yeast, several PMPs traffic via the ER in a Pex3- and Pex19-dependent manner. In Komagataella phaffii (formerly called Pichia pastoris) specifically, the indirect traffic of Pex2, but not of Pex11 or Pex17, depends on Pex3, but all PMPs tested for indirect trafficking require Pex19...
November 24, 2017: Journal of Molecular Biology
https://read.qxmd.com/read/28640802/peroxisomal-biogenesis-is-genetically-and-biochemically-linked-to-carbohydrate-metabolism-in-drosophila-and-mouse
#24
JOURNAL ARTICLE
Michael F Wangler, Yu-Hsin Chao, Vafa Bayat, Nikolaos Giagtzoglou, Abhijit Babaji Shinde, Nagireddy Putluri, Cristian Coarfa, Taraka Donti, Brett H Graham, Joseph E Faust, James A McNew, Ann Moser, Marco Sardiello, Myriam Baes, Hugo J Bellen
Peroxisome biogenesis disorders (PBD) are a group of multi-system human diseases due to mutations in the PEX genes that are responsible for peroxisome assembly and function. These disorders lead to global defects in peroxisomal function and result in severe brain, liver, bone and kidney disease. In order to study their pathogenesis we undertook a systematic genetic and biochemical study of Drosophila pex16 and pex2 mutants. These mutants are short-lived with defects in locomotion and activity. Moreover these mutants exhibit severe morphologic and functional peroxisomal defects...
June 2017: PLoS Genetics
https://read.qxmd.com/read/28594894/micrornas-upregulated-during-hiv-infection-target-peroxisome-biogenesis-factors-implications-for-virus-biology-disease-mechanisms-and-neuropathology
#25
JOURNAL ARTICLE
Zaikun Xu, Eugene L Asahchop, William G Branton, Benjamin B Gelman, Christopher Power, Tom C Hobman
HIV-associated neurocognitive disorders (HAND) represent a spectrum neurological syndrome that affects up to 25% of patients with HIV/AIDS. Multiple pathogenic mechanisms contribute to the development of HAND symptoms including chronic neuroinflammation and neurodegeneration. Among the factors linked to development of HAND is altered expression of host cell microRNAs (miRNAs) in brain. Here, we examined brain miRNA profiles among HIV/AIDS patients with and without HAND. Our analyses revealed differential expression of 17 miRNAs in brain tissue from HAND patients...
June 2017: PLoS Pathogens
https://read.qxmd.com/read/28440896/genome-wide-meta-analysis-identifies-a-novel-susceptibility-signal-at-cacna2d3-for-nicotine-dependence
#26
JOURNAL ARTICLE
Xianyong Yin, Chris Bizon, Jeffrey Tilson, Yuan Lin, Ian R Gizer, Cindy L Ehlers, Kirk C Wilhelmsen
Nicotine dependence (ND) has a reported heritability of 40-70%. Low-coverage whole-genome sequencing was conducted in 1,889 samples from the UCSF Family study. Linear mixed models were used to conduct genome-wide association (GWA) tests of ND in this and five cohorts obtained from the database of Genotypes and Phenotypes. Fixed-effect meta-analysis was carried out separately for European (n = 14,713) and African (n = 3,369) participants, and then in a combined analysis of both ancestral groups. The meta-analysis of African participants identified a significant and novel susceptibility signal (rs56247223; p = 4...
April 25, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://read.qxmd.com/read/27799549/e3-ubiquitin-ligase-sp1-regulates-peroxisome-biogenesis-in-arabidopsis
#27
JOURNAL ARTICLE
Ronghui Pan, John Satkovich, Jianping Hu
Peroxisomes are ubiquitous eukaryotic organelles that play pivotal roles in a suite of metabolic processes and often act coordinately with other organelles, such as chloroplasts and mitochondria. Peroxisomes import proteins to the peroxisome matrix by peroxins (PEX proteins), but how the function of the PEX proteins is regulated is poorly understood. In this study, we identified the Arabidopsis RING (really interesting new gene) type E3 ubiquitin ligase SP1 [suppressor of plastid protein import locus 1 (ppi1) 1] as a peroxisome membrane protein with a regulatory role in peroxisome protein import...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/27744104/suppressive-subtractive-hybridization-reveals-different-gene-expression-between-high-and-low-virulence-strains-of-cladosporium-cladosporioides
#28
COMPARATIVE STUDY
Yu Gu, Yanfang Liu, Sanjie Cao, Xiaobo Huang, Zhicai Zuo, Shumin Yu, Junliang Deng, Chunbang Ding, Ming Yuan, Liuhong Shen, Rui Wu, Yiping Wen, Zhihua Ren, Qin Zhao, Guangneng Peng, Zhijun Zhong, Chengdong Wang, Xiaoping Ma
Cladosporium cladosporioides is a ubiquitous fungus, causing infections in plants, humans, and animals. Suppression subtractive hybridization (SSH) and quantitative real-time PCR (qRT-PCR) were used in this study to identify differences in gene expression between two C. cladosporioides strains, the highly virulent Z20 strain and the lowly virulent Zt strain. A total of 61 unigenes from the forward library and 42 from the reverse library were identified. Gene ontology (GO) analysis showed that these genes were involved in various biological processes, cellular components and molecular functions...
November 2016: Microbial Pathogenesis
https://read.qxmd.com/read/27650450/genetic-interactions-between-peroxin12-and-other-peroxisome-associated-ubiquitination-components
#29
JOURNAL ARTICLE
Yun-Ting Kao, Wendell A Fleming, Meredith J Ventura, Bonnie Bartel
Most eukaryotic cells require peroxisomes, organelles housing fatty acid β-oxidation and other critical metabolic reactions. Peroxisomal matrix proteins carry peroxisome-targeting signals that are recognized by one of two receptors, PEX5 or PEX7, in the cytosol. After delivering the matrix proteins to the organelle, these receptors are removed from the peroxisomal membrane or matrix. Receptor retrotranslocation not only facilitates further rounds of matrix protein import but also prevents deleterious PEX5 retention in the membrane...
November 2016: Plant Physiology
https://read.qxmd.com/read/27597759/pex2-is-the-e3-ubiquitin-ligase-required-for-pexophagy-during-starvation
#30
JOURNAL ARTICLE
Graeme Sargent, Tim van Zutphen, Tatiana Shatseva, Ling Zhang, Valeria Di Giovanni, Robert Bandsma, Peter Kijun Kim
Peroxisomes are metabolic organelles necessary for anabolic and catabolic lipid reactions whose numbers are highly dynamic based on the metabolic need of the cells. One mechanism to regulate peroxisome numbers is through an autophagic process called pexophagy. In mammalian cells, ubiquitination of peroxisomal membrane proteins signals pexophagy; however, the E3 ligase responsible for mediating ubiquitination is not known. Here, we report that the peroxisomal E3 ubiquitin ligase peroxin 2 (PEX2) is the causative agent for mammalian pexophagy...
September 12, 2016: Journal of Cell Biology
https://read.qxmd.com/read/27378168/8q21-11-microdeletion-in-two-patients-with-syndromic-peters-anomaly
#31
REVIEW
Hannah Happ, Kala F Schilter, Eric Weh, Linda M Reis, Elena V Semina
Peters anomaly is a form of anterior segment dysgenesis characterized by central ocular opacity and corneo-lenticular adhesions. Isolated and syndromic Peters anomaly can be observed and demonstrate significant genetic heterogeneity. We report the identification of overlapping 8q21.11 deletions in two patients with syndromic Peters anomaly via whole exome sequencing and chromosomal microarray analyses. Microdeletions of 8q21.11 were recently reported in 10 patients with highly variable phenotypes involving craniofacial features, ptosis, intellectual disability, abnormalities of the hands/feet and other defects; sclerocornea and/or microphthalmia were reported in three cases...
September 2016: American Journal of Medical Genetics. Part A
https://read.qxmd.com/read/27230853/expanding-the-spectrum-of-pex10-related-peroxisomal-biogenesis-disorders-slowly-progressive-recessive-ataxia
#32
JOURNAL ARTICLE
Mathilde Renaud, Claire Guissart, Martial Mallaret, Sacha Ferdinandusse, David Cheillan, Nathalie Drouot, Jean Muller, Mireille Claustres, Christine Tranchant, Mathieu Anheim, Michel Koenig
Peroxisomal biogenesis disorders (PBDs) consist of a heterogeneous group of autosomal recessive diseases, in which peroxisome assembly and proliferation are impaired leading to severe multisystem disease and early death. PBDs include Zellweger spectrum disorders (ZSDs) with a relatively mild clinical phenotype caused by PEX1, (MIM# 602136), PEX2 (MIM# 170993), PEX6 (MIM# 601498), PEX10 (MIM# 602859), PEX12 (MIM# 601758), and PEX16 (MIM# 603360) mutations. Three adult patients are reported belonging to a non-consanguineous French family affected with slowly progressive cerebellar ataxia, axonal neuropathy, and pyramidal signs...
August 2016: Journal of Neurology
https://read.qxmd.com/read/26833788/distinct-requirements-for-intra-er-sorting-and-budding-of-peroxisomal-membrane-proteins-from-the-er
#33
JOURNAL ARTICLE
Gaurav Agrawal, Scott N Fassas, Zhi-Jie Xia, Suresh Subramani
During de novo peroxisome biogenesis, importomer complex proteins sort via two preperoxisomal vesicles (ppVs). However, the sorting mechanisms segregating peroxisomal membrane proteins to the preperoxisomal endoplasmic reticulum (pER) and into ppVs are unknown. We report novel roles for Pex3 and Pex19 in intra-endoplasmic reticulum (ER) sorting and budding of the RING-domain peroxins (Pex2, Pex10, and Pex12). Pex19 bridged the interaction at the ER between Pex3 and RING-domain proteins, resulting in a ternary complex that was critical for the intra-ER sorting and subsequent budding of the RING-domain peroxins...
February 1, 2016: Journal of Cell Biology
https://read.qxmd.com/read/26644511/yeast-pex1-cells-contain-peroxisomal-ghosts-that-import-matrix-proteins-upon-reintroduction-of-pex1
#34
JOURNAL ARTICLE
Kèvin Knoops, Rinse de Boer, Anita Kram, Ida J van der Klei
Pex1 and Pex6 are two AAA-ATPases that play a crucial role in peroxisome biogenesis. We have characterized the ultrastructure of the Saccharomyces cerevisiae peroxisome-deficient mutants pex1 and pex6 by various high-resolution electron microscopy techniques. We observed that the cells contained peroxisomal membrane remnants, which in ultrathin cross sections generally appeared as double membrane rings. Electron tomography revealed that these structures consisted of one continuous membrane, representing an empty, flattened vesicle, which folds into a cup shape...
December 7, 2015: Journal of Cell Biology
https://read.qxmd.com/read/26376864/gene-based-meta-analysis-of-genome-wide-association-studies-implicates-new-loci-involved-in-obesity
#35
JOURNAL ARTICLE
Sara Hägg, Andrea Ganna, Sander W Van Der Laan, Tonu Esko, Tune H Pers, Adam E Locke, Sonja I Berndt, Anne E Justice, Bratati Kahali, Marten A Siemelink, Gerard Pasterkamp, David P Strachan, Elizabeth K Speliotes, Kari E North, Ruth J F Loos, Joel N Hirschhorn, Yudi Pawitan, Erik Ingelsson
To date, genome-wide association studies (GWASs) have identified >100 loci with single variants associated with body mass index (BMI). This approach may miss loci with high allelic heterogeneity; therefore, the aim of the present study was to use gene-based meta-analysis to identify regions with high allelic heterogeneity to discover additional obesity susceptibility loci. We included GWAS data from 123 865 individuals of European descent from 46 cohorts in Stage 1 and Metabochip data from additional 103 046 individuals from 43 cohorts in Stage 2, all within the Genetic Investigation of ANthropometric Traits (GIANT) consortium...
December 1, 2015: Human Molecular Genetics
https://read.qxmd.com/read/26367802/the-birth-of-yeast-peroxisomes
#36
REVIEW
Wei Yuan, Marten Veenhuis, Ida J van der Klei
This contribution describes the phenotypic differences of yeast peroxisome-deficient mutants (pex mutants). In some cases different phenotypes were reported for yeast mutants deleted in the same PEX gene. These differences are most likely related to the marker proteins and methods used to detect peroxisomal remnants. This is especially evident for pex3 and pex19 mutants, where the localization of receptor docking proteins (Pex13, Pex14) resulted in the identification of peroxisomal membrane remnants, which do not contain other peroxisomal membrane proteins, such as the ring proteins Pex2, Pex10 and Pex12...
May 2016: Biochimica et Biophysica Acta
https://read.qxmd.com/read/25287989/associations-between-menarche-related-genetic-variants-and-pubertal-growth-in-male-and-female-adolescents
#37
JOURNAL ARTICLE
Wanzhu Tu, Erin K Wagner, George J Eckert, Zhangsheng Yu, Tamara Hannon, J Howard Pratt, Chunyan He
PURPOSE: Previous studies have identified novel genetic variants associated with age at menarche in females of European descent. The pubertal growth effects of these variants have not been carefully evaluated in non-European descent groups. We aimed to examine the effects of 31 newly identified menarche-related single-nucleotide polymorphisms (SNPs) on growth outcomes in African-American (AA) and European-American (EA) children in a prospective cohort. METHODS: We analyzed longitudinal data collected from 263 AAs and 338 EAs enrolled between ages 5 and 17 years; the subjects were followed semiannually for an average of 6 years...
January 2015: Journal of Adolescent Health
https://read.qxmd.com/read/25248106/ectopic-expression-of-the-ring-domain-of-the-arabidopsis-peroxin2-protein-partially-suppresses-the-phenotype-of-the-photomorphogenic-mutant-de-etiolated1
#38
JOURNAL ARTICLE
Mintu Desai, Navneet Kaur, Jianping Hu
The Arabidopsis constitutive photomorphogenic/de-etiolated 1/FUSCA (COP/DET1/FUS) proteins repress photomorphogenesis by degrading positive regulators of photomorphogenesis, such as the transcription factor long hypocotyl5 (HY5). The gain-of-function mutant ted3, which partially suppresses the det1 mutant, contains a missense mutation of a Val-to-Met substitution before the C-terminal RING finger domain of the peroxisomal membrane protein peroxin2 (PEX2). We hypothesized that a truncated PEX2 protein, which only contains the C-terminal RING domain, is initiated by the ted3 mutation and by-passes the function of DET1 in the nucleus...
2014: PloS One
https://read.qxmd.com/read/25214533/peroxisomal-ubiquitin-protein-ligases-peroxin2-and-peroxin10-have-distinct-but-synergistic-roles-in-matrix-protein-import-and-peroxin5-retrotranslocation-in-arabidopsis
#39
JOURNAL ARTICLE
Sarah E Burkhart, Yun-Ting Kao, Bonnie Bartel
Peroxisomal matrix proteins carry peroxisomal targeting signals (PTSs), PTS1 or PTS2, and are imported into the organelle with the assistance of peroxin (PEX) proteins. From a microscopy-based screen to identify Arabidopsis (Arabidopsis thaliana) mutants defective in matrix protein degradation, we isolated unique mutations in PEX2 and PEX10, which encode ubiquitin-protein ligases anchored in the peroxisomal membrane. In yeast (Saccharomyces cerevisiae), PEX2, PEX10, and a third ligase, PEX12, ubiquitinate a peroxisome matrix protein receptor, PEX5, allowing the PEX1 and PEX6 ATP-hydrolyzing enzymes to retrotranslocate PEX5 out of the membrane after cargo delivery...
November 2014: Plant Physiology
https://read.qxmd.com/read/24358884/proteins-and-lipids-of-glycosomal-membranes-from-leishmania-tarentolae-and-trypanosoma-brucei
#40
JOURNAL ARTICLE
Claudia Colasante, Frank Voncken, Theresa Manful, Thomas Ruppert, Aloysius G M Tielens, Jaap J van Hellemond, Christine Clayton
In kinetoplastid protists, several metabolic pathways, including glycolysis and purine salvage, are located in glycosomes, which are microbodies that are evolutionarily related to peroxisomes. With the exception of some potential transporters for fatty acids, and one member of the mitochondrial carrier protein family, proteins that transport metabolites across the glycosomal membrane have yet to be identified. We show here that the phosphatidylcholine species composition of Trypanosoma brucei glycosomal membranes resembles that of other cellular membranes, which means that glycosomal membranes are expected to be impermeable to small hydrophilic molecules unless transport is facilitated by specialized membrane proteins...
2013: F1000Research
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