Peroxisomal Proteostasis Involves a Lon Family Protein That Functions as Protease and Chaperone

Proteins are subject to continuous quality control for optimal proteostasis. The knowledge of peroxisome quality control systems is still in its infancy. Here we show that peroxisomes contain a member of the Lon family of proteases (Pln). We show that Pln is a heptameric protein and acts as an ATP-fueled protease and chaperone. Hence, Pln is the first chaperone identified in fungal peroxisomes. In cells of a PLN deletion strain peroxisomes contain protein aggregates, a major component of which is catalase-peroxidase. We show that this enzyme is sensitive to oxidative damage. The oxidatively damaged, but not the native protein, is a substrate of the Pln protease. Cells of the pln strain contain enhanced levels of catalase-peroxidase protein but reduced catalase-peroxidase enzyme activities. Together with the observation that Pln has chaperone activity in vitro, our data suggest that catalase-peroxidase aggregates accumulate in peroxisomes of pln cells due to the combined absence of Pln protease and chaperone activities.

Critical phenomena and universal dynamics in one-dimensional driven diffusive systems with two species of particles

Recent work on stochastic interacting particle systems with two particle species (or single-species systems with kinematic constraints) has demonstrated the existence of spontaneous symmetry breaking, long-range order and phase coexistence in nonequilibrium steady states, even if translational invariance is not broken by defects or open boundaries. If both particle species are conserved, the temporal behaviour is largely unexplored, but first results of current work on the transition from the microscopic to the macroscopic scale yield exact coupled nonlinear hydrodynamic equations and indicate the emergence of novel types of shock waves which are collective excitations stabilized by the flow of microscopic fluctuations. We review the basic stationary and dynamic properties of these systems, highlighting the role of conservation laws and kinetic constraints for the hydrodynamic behaviour, the microscopic origin of domain wall (shock) stability and the coarsening dynamics of domains during phase separation.Comment: 72 pages, 6 figures, 201 references (topical review for J. Phys. A: Math. Gen.

Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

addresses: Peninsula College of Medicine and Dentistry, St Luke's Campus, University of Exeter, Exeter, UK. [email protected]: PMCID: PMC3528446types: Journal Article; Research Support, Non-U.S. Gov't© 2012 Warren et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention

Proteomic Analysis of Mitochondrial Protein Turnover: Identification of Novel Substrate Proteins of the Matrix Protease Pim1

ATP-dependent oligomeric proteases are major components of cellular protein quality control systems. To investigate the role of proteolytic processes in the maintenance of mitochondrial functions, we analyzed the dynamic behavior of the mitochondrial proteome of Saccharomyces cerevisiae by two-dimensional (2D) polyacrylamide gel electrophoresis. By a characterization of the influence of temperature on protein turnover in isolated mitochondria, we were able to define four groups of proteins showing a differential susceptibility to proteolysis. The protein Pim1/LON has been shown to be the main protease in the mitochondrial matrix responsible for the removal of damaged or nonnative proteins. To assess the substrate range of Pim1 under in vivo conditions, we performed a quantitative comparison of the 2D protein spot patterns between wild-type and pim1Δ mitochondria. We were able to identify a novel subset of mitochondrial proteins that are putative endogenous substrates of Pim1. Using an in organello degradation assay, we confirmed the Pim1-specific, ATP-dependent proteolysis of the newly identified substrate proteins. We could demonstrate that the functional integrity of the Pim1 substrate proteins, in particular, the presence of intact prosthetic groups, had a major influence on the susceptibility to proteolysis

Influence of the cholinergic agonist RS 86 on normal sleep: sex and age effects

In 36 healthy control subjects (21 females, 15 males; age range 18-65 years; mean age 41.8 years, SD 15.6 years), a bedtime dose of 1.5 mg RS 86, an orally acting cholinergic agonist, shortened rapid eye movement (REM) latency, increased REM sleep, and decreased slow-wave sleep. Six of the subjects (greater than 40 years old) even displayed sleep-onset REM periods after the drug. Results of the present study agree well with those of studies using other cholinomimetics (i.e., physostigmine, arecholine) and confirm the importance of the cholinergic system for REM sleep regulation. Since RS 86 mimicked some of the REM sleep abnormalities specific for patients with depressive disorders, the cholinergic system may play a role in the pathogenesis and pathophysiology of depressive diseases