Conserved targeting information in mammalian and fungal peroxisomal tail-anchored proteins

The targeting signals and mechanisms of soluble peroxisomal proteins are well understood, whereas less is known about the signals and targeting routes of peroxisomal membrane proteins (PMP). Pex15 and PEX26, tail-anchored proteins in yeast and mammals, respectively, exert a similar cellular function in the recruitment of AAA peroxins at the peroxisomal membrane. But despite their common role, Pex15 and PEX26 are neither homologs nor they are known to follow similar targeting principles. Here we show that Pex15 targets to peroxisomes in mammalian cells, and PEX26 reaches peroxisomes when expressed in yeast cells. In both proteins C-terminal targeting information is sufficient for correct sorting to the peroxisomal membrane. In yeast, PEX26 follows the pathway that also ensures correct targeting of Pex15: PEX26 enters the endoplasmic reticulum (ER) in a GET-dependent and Pex19-independent manner. Like in yeast, PEX26 enters the ER in mammalian cells, however, independently of GET/TRC40. These data show that conserved targeting information is employed in yeast and higher eukaryotes during the biogenesis of peroxisomal tail-anchored proteins

Conserved targeting information in mammalian and fungal peroxisomal tail-anchored proteins

The targeting signals and mechanisms of soluble peroxisomal proteins are well understood, whereas less is known about the signals and targeting routes of peroxisomal membrane proteins (PMP). Pex15 and PEX26, tail-anchored proteins in yeast and mammals, respectively, exert a similar cellular function in the recruitment of AAA peroxins at the peroxisomal membrane. But despite their common role, Pex15 and PEX26 are neither homologs nor they are known to follow similar targeting principles. Here we show that Pex15 targets to peroxisomes in mammalian cells, and PEX26 reaches peroxisomes when expressed in yeast cells. In both proteins C-terminal targeting information is sufficient for correct sorting to the peroxisomal membrane. In yeast, PEX26 follows the pathway that also ensures correct targeting of Pex15: PEX26 enters the endoplasmic reticulum (ER) in a GET-dependent and Pex19-independent manner. Like in yeast, PEX26 enters the ER in mammalian cells, however, independently of GET/TRC40. These data show that conserved targeting information is employed in yeast and higher eukaryotes during the biogenesis of peroxisomal tail-anchored proteins

Characterization of two common 5' polymorphisms in PEX1 and correlation to survival in PEX1 peroxisome biogenesis disorder patients

<p>Abstract</p> <p>Background</p> <p>Mutations in PEX1 are the most common primary cause of Zellweger syndrome. In addition to exonic mutations, deletions and splice site mutations two 5' polymorphisms at c.-137 and c.-53 with a potential influence on PEX1 protein levels have been described in the 5' untranslated region (UTR) of the <it>PEX1 </it>gene.</p> <p>Methods</p> <p>We used RACE and in silico promoter prediction analysis to study the 5' UTR of <it>PEX1</it>. We determined the distribution of <it>PEX1 </it>5' polymorphisms in a cohort of 30 Zellweger syndrome patients by standard DNA sequencing. 5' polymorphisms were analysed in relation to the two most common mutations in <it>PEX1 </it>and were incorporated into a novel genotype-phenotype analysis by correlation of three classes of <it>PEX1 </it>mutations with patient survival.</p> <p>Results</p> <p>We provide evidence that the polymorphism 137 bp upstream of the ATG codon is not part of the UTR, rendering it a promoter polymorphism. We show that the first, but not the second most common <it>PEX1 </it>mutation arose independently of a specific upstream polymorphic constellation. By genotype-phenotype analysis we identified patients with identical exonic mutation and identical 5' polymorphisms, but strongly differing survival.</p> <p>Conclusions</p> <p>Our study suggests that two different types of <it>PEX1 </it>5' polymorphisms have to be distinguished: a 5' UTR polymorphism at position c.-53 and a promoter polymorphism 137 bp upstream of the PEX1 start codon. Our results indicate that the exonic <it>PEX1 </it>mutation correlates with patient survival, but the two 5' polymorphisms analysed in this study do not have to be considered for diagnostic and/or prognostic purposes.</p

Разработка технологии восстановления деталей автомобилей и тракторов с последующим упрочнением пластическим деформированием.

В разделе объект и методы исследования выполнен аналитический обзор по теме работы и обоснован выбор темы выпускной работы бакалавра. В разделе расчеты и аналитика представлены необходимые инженерные расчеты, связанные с организацией работ по восстановлению распределительного вала двигателя КамАЗ-740. В разделе "Социальная ответственность" выявлены опасные и вредныеIn the section of the object and methods of research, an analytical review of the topic of work was carried out and the choice of the topic of the bachelor's thesis was substantiated. The calculations and analytics section presents the necessary engineering calculations related to the organization of work on the restoration of the camshaft of the KAMAZ-740 engine. In the section "Social responsibility" identified dangerous and harmful factors, as well as measures for their elimination. The section “Financial Management, Resource Efficiency and Resource Saving” provides an economic assessment of design decisions. The final qualifying work was done in the text editor Microsoft Word 2007 and the graphical editor KOMPAS 3D V16.

Glial β-Oxidation regulates drosophila energy metabolism

The brain's impotence to utilize long-chain fatty acids as fuel, one of the dogmas in neuroscience, is surprising, since the nervous system is the tissue most energy consuming and most vulnerable to a lack of energy. Challenging this view, we here show in vivo that loss of the Drosophila carnitine palmitoyltransferase 2 (CPT2), an enzyme required for mitochondrial β-oxidation of long-chain fatty acids as substrates for energy production, results in the accumulation of triacylglyceride-filled lipid droplets in adult Drosophila brain but not in obesity. CPT2 rescue in glial cells alone is sufficient to restore triacylglyceride homeostasis, and we suggest that this is mediated by the release of ketone bodies from the rescued glial cells. These results demonstrate that the adult brain is able to catabolize fatty acids for cellular energy production.This work was partially supported by the Flanders Fund for Scientific Research (FWO G 0.666.10N), NEUROBRAINNET IAP 7/16, Flemish Government Methusalem Grant, Spanish Ministry of Science (SAF2010-14906) and Innovation Ingenio-Consolider (CSD2010-00045) and Spanish Ministry of Economy and Competitiveness (SAF2013-45392).Peer Reviewe

Glial β-Oxidation regulates drosophila energy metabolism

The brain's impotence to utilize long-chain fatty acids as fuel, one of the dogmas in neuroscience, is surprising, since the nervous system is the tissue most energy consuming and most vulnerable to a lack of energy. Challenging this view, we here show in vivo that loss of the Drosophila carnitine palmitoyltransferase 2 (CPT2), an enzyme required for mitochondrial β-oxidation of long-chain fatty acids as substrates for energy production, results in the accumulation of triacylglyceride-filled lipid droplets in adult Drosophila brain but not in obesity. CPT2 rescue in glial cells alone is sufficient to restore triacylglyceride homeostasis, and we suggest that this is mediated by the release of ketone bodies from the rescued glial cells. These results demonstrate that the adult brain is able to catabolize fatty acids for cellular energy production.This work was partially supported by the Flanders Fund for Scientific Research (FWO G 0.666.10N), NEUROBRAINNET IAP 7/16, Flemish Government Methusalem Grant, Spanish Ministry of Science (SAF2010-14906) and Innovation Ingenio-Consolider (CSD2010-00045) and Spanish Ministry of Economy and Competitiveness (SAF2013-45392).Peer Reviewe