Double-edged alliance: mitochondrial surveillance by the UPS and autophagy

Mitochondria provide an essential role in the maintenance of cellular homeostasis with regard to energy generation, redox signaling, and programmed cell death. Consequently, fast adaptation to metabolic changes associated with developmental demands or stress induction requires a balanced coordination of mitochondrial biogenesis and removal of damaged mitochondria. Impaired mitochondrial maintenance is causally linked to many human pathologies and aging, including diabetes, cancer, and neurodegenerative diseases. Thus, it is of fundamental importance to understand cellular surveillance mechanisms that support a healthy mitochondrial network. In this review, we discuss the role of ubiquitin-dependent protein degradation in mitochondrial functionality

A fitokróm fotoreceptorok indukálta jelátviteli lánc molekuláris vizsgálata Arabidopsis thalianában = Molecular analysis of phytochrome induced signal transduction in Arabidopsis thaliana

Bebizonyítottuk, hogy a fitokróm-A sejtmagba történő transzlokációjában és sejtmagi akkumulációjában, tehát a fitokróm-A szabályozta jelátviteli lánc aktiválásában az FHY1 fehérje meghatározó szerepet játszik. Kimutattuk, hogy a fitokróm-A autofoszforilációja negatívan szabályozza a jelátviteli lánc aktivitását és azonosítottunk egy olyan foszfatázt, ami specifikusan a fitokróm-A fotoreceptor defoszforilációjáért felelős. Bebizonyítottuk, hogy a PIF3 fehérje nem pozitív, hanem negatív regulátora a fotomorfogenezisnek, a PIF3 fehérje nem szükséges a cirkadián óra működéséhez, továbbá, hogy fény hatására a PIF3 fehérje gyorsan degradálódik és hogy a fitokróm- A-B és D fotoreceptorok együttesen szabályozzák a PIF3 transzkripciós faktor fény indukálta degradációját. | We have provided compelling evidence that nuclear translocation and accumulation of phytochrome-A requires the FHY1 protein and that FHY1 interacts with the phyA molecule in a conformation dependent fashion and this interaction is mediated by the very N-terminal domain of the photoreceptor. We demonstrated that PIF3 transcription factor negatively regulates phytochrome controlled photomorphogenesis, its function is not required for light dependent entrainment of the plant circadian clock and that phytochrome-A in harmony with phytochrome-B and D regulates light induced degradation of PIF3. Moreover, we showed that interaction of phytochrome-A with various components of the phytochrome-A dependent signalling cascade is negatively regulated by the autophosphorylation of the photoreceptor and that dephosphorylation of the photoreceptor is mediated by a specific phosphatase

Aszimptotikus approximációk a sztochasztikában = Asymptotic approximations in stochastics

Csörgő Sándor kutatásainak középpontjában a szentpétervári játék vizsgálata állt. Eredményeinek jelentős része az osztozkodási stratégiákhoz kapcsolódik. Az elért aszimptotikus eredmények nagymértékben hozzájárulnak a játékkal kapcsolatos számos probléma tisztázásához. Pósfai Anna az úgynevezett kupongyűjtő problémához köthető speciális határeloszlás tételeket finomította. A gyűjtő várakozási idejének nevezett véletlen mennyiség eloszlását négy jólismert eloszláscsalád tagjaival approximálta, és a kapcsolódó eloszlásfüggvényeknek aszimptotikus sorfejtéseit adta. Kevei Péter független, azonos eloszlású véletlen változók összegének illetve lineáris kombinációinak aszimptotikus viselkedését vizsgálta, különös tekintettel a szemistablis eloszlásokra és a szentpétervári játékra. Szabó Tamás és Krauczi Éva a Wasserstein távolságra épülő korrelációs tesztekkel foglalkoztak. Meghatározták a tesztstatisztikák határeloszlásait. Szimulációs vizsgálatokkal ellenőrizték a tesztek hatékonyságát. Szűcs Gábor kutatási területe az empirikus folyamatok approximációinak elmélete. Legfontosabb eredménye a valószínűségi generátorfüggvények segítségével felírt empirikus generátorfolyamatok eloszlásbeli konvergenciájára vonatkozik. Viharos László a TTT folyamat felhasználásával hatékony tesztet konstruált egy összetett illeszkedési hipotézis vizsgálatára. Pareto eloszlások indexének becslésével is foglalkozott. | Sándor Csörgő's main research field was the St. Petersburg game. A substantial part of his results concerns the pooling strategies. The obtained asymptotic results help to clarify several problems connected to the game. Anna Pósfai refined certain special limit theorems related to the so-called coupon collector's problem. She approximated the distribution of the random quantity called the collector's waiting time with the members of four well-known distribution families, and gave asymptotic expansions of the related distribution functions. Péter Kevei investigated the asymptotic behavior of sums and linear combinations of independent, identically distributed random variables, especially considering semistable laws, and the St. Petersburg game. Tamás Szabó and Éva Krauczi investigated correlation tests based on the Wasserstein distance. They derived the limit distributions of the test statistics. They performed simulation studies to check the efficiency of the tests. Gábor Szűcs's research field is the theory of approximation of empirical processes. His main result concerns the convergence in distribution of empirical generator processes defined via probability generating functions. Based on the TTT process, László Viharos constructed an efficient test to check a composite goodness-of-fit hypothesis. Moreover, he studied estimation of the index of Pareto distributions

The ubiquitin ligase CHIP integrates proteostasis and aging by regulation of insulin receptor turnover

Aging is attended by a progressive decline in protein homeostasis (proteostasis), aggravating the risk for protein aggregation diseases. To understand the coordination between proteome imbalance and longevity, we addressed the mechanistic role of the quality-control ubiquitin ligase CHIP, which is a key regulator of proteostasis. We observed that CHIP deficiency leads to increased levels of the insulin receptor (INSR) and reduced lifespan of worms and flies. The membrane-bound INSR regulates the insulin and IGF1 signaling (IIS) pathway and thereby defines metabolism and aging. INSR is a direct target of CHIP, which triggers receptor monoubiquitylation and endocytic-lysosomal turnover to promote longevity. However, upon proteotoxic stress conditions and during aging, CHIP is recruited toward disposal of misfolded proteins, reducing its capacity to degrade the INSR. Our study indicates a competitive relationship between proteostasis and longevity regulation through CHIP-assisted proteolysis, providing a mechanistic concept for understanding the impact of proteome imbalance on aging

Ubiquitin sets the timer: impacts on aging and longevity

Protein homeostasis is essential for cellular function, organismal growth and viability. Damaged and aggregated proteins are turned over by two major proteolytic routes of the cellular quality-control pathways: the ubiquitin-proteasome system and autophagy. For both these pathways, ubiquitination provides the recognition signal for substrate selection. This Commentary discusses how ubiquitin-dependent proteolytic pathways are coordinated with stress- and aging-induced signals

E4 ligase–specific ubiquitination hubs coordinate DNA double-strand-break repair and apoptosis

Multiple protein ubiquitination events at DNA double-strand breaks (DSBs) regulate damage recognition, signaling and repair. It has remained poorly understood how the repair process of DSBs is coordinated with the apoptotic response. Here, we identified the E4 ubiquitin ligase UFD-2 as a mediator of DNA-damage-induced apoptosis in a genetic screen in Caenorhabditis elegans. We found that, after initiation of homologous recombination by RAD-51, UFD-2 forms foci that contain substrate-processivity factors including the ubiquitin-selective segregase CDC-48 (p97), the deubiquitination enzyme ATX-3 (Ataxin-3) and the proteasome. In the absence of UFD-2, RAD-51 foci persist, and DNA damage-induced apoptosis is prevented. In contrast, UFD-2 foci are retained until recombination intermediates are removed by the Holliday-junction-processing enzymes GEN-1, MUS-81 or XPF-1. Formation of UFD-2 foci also requires proapoptotic CEP-1 (p53) signaling. Our findings establish a central role of UFD-2 in the coordination between the DNA-repair process and the apoptotic response

Analysis of genetic variability within the genus Petromyces

Phenotypic and genotypic features of three teleomorphic species, Petromyces alliaceus, P. albertensis and P. muricatus and some related anamorphic Aspergillus species were compared. The dendrogram based on carbon source utilisation data revealed a close relationship between P. muricatus and the A. ochraceus strains examined. P. alliaceus and P. albertensis strains were very closely related to each other. A dendrogram with similar topology was obtained by analysing sequences of the intergenic transcribed spacer regions of representatives of these species. P. alliaceus and P. albertensis strains could only be distinguished by the random amplified polymorphic DNA technique. These strains possibly represent a single species closely related to Aspergillus section Flavi, while the anamorph of P. muricatus is a member of Aspergillus section Circumdati. Our results indicate that Aspergillus section Circumdati is in need of taxonomic revision

Circadian Clock-Regulated Expression of Phytochrome and Cryptochrome Genes in Arabidopsis

Many physiological and biochemical processes in plants exhibit endogenous rhythms with a period of about 24 h. Endogenous oscillators called circadian clocks regulate these rhythms. The circadian clocks are synchronized to the periodic environmental changes (e.g. day/night cycles) by specific stimuli; among these, the most important is the light. Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock by transducing the light signal to the central oscillator. In this work, we analyzed the spatial, temporal, and long-term light-regulated expression patterns of the Arabidopsis phytochrome (PHYA to PHYE) and cryptochrome (CRY1 and CRY2) promoters fused to the luciferase (LUC(+)) reporter gene. The results revealed new details of the tissue-specific expression and light regulation of the PHYC and CRY1 and 2 promoters. More importantly, the data obtained demonstrate that the activities of the promoter::LUC(+) constructs, with the exception of PHYC::LUC(+), display circadian oscillations under constant conditions. In addition, it is shown by measuring the mRNA abundance of PHY and CRY genes under constant light conditions that the circadian control is also maintained at the level of mRNA accumulation. These observations indicate that the plant circadian clock controls the expression of these photoreceptors, revealing the formation of a new regulatory loop that could modulate gating and resetting of the circadian clock