Merrittbech3356

In the past three decades, significant advances have been made in providing the biochemical background of TOM-mediated protein translocation into mitochondria. In the light of recent cryoelectron microscopy-derived structures of TOM isolated from Neurospora crassa and Saccharomyces cerevisiae, the interpretation of biochemical and biophysical studies of TOMmediated protein transport into mitochondria now rests on a solid basis. In this review, we compare the sub-nanometer structure of N. crassa TOM core complex with that of yeast. Both structures reveal remarkably well-conserved symmetrical dimers of ten membrane protein subunits. The structural data also validate predictions of weakly stable regions in the transmembrane β-barrel domains of the protein-conducting subunit Tom40, which signal the existence of β-strands located in interfaces of protein-protein interactions.The evolution of mitochondrial protein import and the systems that mediate it marks the boundary between the endosymbiotic ancestor of mitochondria and a true organelle that is under the control of the nucleus. Protein import has been studied in great detail in Saccharomyces cerevisiae. More recently it has also been extensively investigated in the parasitic protozoan Trypanosoma brucei making it arguably the second best studied system. Here I provide a comparative analysis of the protein import complexes of yeast and trypanosomes. Together with data from other systems, this allows to reconstruct the ancestral features of import complexes that were present in the last eukaryotic common ancestor (LECA) and to identify which subunits were added later in evolution. I discuss how these data can be translated into plausible scenarios providing insights into the evolution of (i) outer membrane protein import receptors, (ii) proteins involved in biogenesis of α-helically anchored outer membrane proteins, and (iii) of the intermembrane space import and assembly system. Finally, I show that the unusual presequence-associated import motor of trypanosomes suggests a scenario of how the two ancestral inner membrane protein translocases present in LECA evolved into the single bifunctional one found in extant trypanosomes.The peptidyl-prolyl cis/trans isomerases (PPIases) Par14 and Par17 result from alternative transcription initiation of the PIN4 gene. read more Whereas Par14 is present in all metazoan, Par17 is only expressed in Hominidae. Par14 resides mainly within the cellular nucleus, while Par17 is translocated into mitochondria. Using photo-affinity labelling, cross-linking and mass spectrometry we identified binding partners for both enzymes from HeLa lysates and disentangled their cellular roles. Par14 is involved in biogenesis of ribonucleoproteincomplexes, RNA processing and DNA repair. Its elongated isoform Par17 participates in protein transport/translocation and in cytoskeleton organization. NMR spectroscopy reveals that Par17 binds to β-actin with its N-terminal region, while both parvulins initiate actin polymerization depending on their PPIase activity as monitored by fluorescence spectroscopy. The knockdown of Par17 in HCT116 cells results in a defect in cell motility and migration.Eukaryotic organisms have evolved complex and robust cellular stress response pathways to ensure maintenance of proteostasis and survival during fluctuating environmental conditions. Highly conserved stress response pathways can be triggered and coordinated at the cell autonomous and cell-non-autonomous level by proteostasis transcription factors, including HSF1, SKN-1/Nrf2, HIF1 and DAF-16/FOXO that combat proteotoxic stress caused by environmental challenges. While these transcription factors are often associated with a specific stress condition, they also direct "non-canonical" transcriptional programmes that serve to integrate a multitude of physiological responses required for development, metabolism and defence responses to pathogen infections. In this review we outline the established function of these key proteostasis transcription factors at the cell-autonomous and cell-non-autonomous level and discuss a newly emerging stress responsive transcription factor, PQM-1, within the proteostasis network. We look beyond the canonical stress response roles of proteostasis transcription factors and highlight their function in integrating different physiological stimuli to maintain cytosolic organismal proteostasis.in English, French, RÉSUMÉ Contexte Aucune étude de données historiques longitudinales sur la contraception n'a cherché à établir si une naissance non planifiée (résultat d'une grossesse non planifiée) était associée à un changement de comportement contraceptif, y compris en Colombie et au Pérou où les niveaux de fécondité non planifiée restent élevés. Méthodes Les données de calendrier historique mensuel ayant trait à la reproduction, extraites des Enquêtes démographiques et de santé 2010 de Colombie et 2012 du Pérou, ont servi à l‘étude du comportement contraceptif de 13 373 et 7 425 femmes, respectivement. Des tables de transition et des modèles de risque ont permis d'identifier les associations entre les méthodes contraceptives utilisées avant et après la grossesse, ainsi que d‘évaluer la différence de ces rapports suivant que les femmes avaient déclaré une naissance non planifiée ou planifiée. Résultats Les femmes qui pratiquaient une méthode traditionnelle, barrière ou (en Colombie) hormonale à courte demmes.This article addresses the event-triggered adaptive fuzzy output-feedback control problem for a class of nonstrict-feedback nonlinear systems with asymmetric and time-varying output constraints, as well as unknown nonlinear functions. By designing a linear observer to estimate the unmeasurable states, a novel event-triggered adaptive fuzzy output-feedback control scheme is proposed. The barrier Lyapunov function (BLF) and the error transformation technique are used to handle the output constraint under a completely unknown initial tracking condition. It is shown that with the proposed control scheme, all the solutions of the closed-loop system are semiglobally bounded, and the tracking error converges to a small set near zero, while the output constraint is satisfied within a predetermined finite time, even when the constraint condition is violated initially. Moreover, with the proposed event-triggering mechanism (ETM), the Zeno behavior can be strictly ruled out. An example is finally provided to demonstrate the effectiveness of the proposed control method.