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1. Species-rich communities exhibit higher levels of ecosystem functioning compared to species-poor ones, and this positive relationship strengthens over time. One proposed explanation for this phenomenon is the reduction of niche overlap among plants or animals, which corresponds to increased complementarity and reduced competition. 2. In order to examine the potential of increased complementarity among plants or animals to strengthen the relationship between diversity and ecosystem functions, we integrated models of bio-energetic population dynamics and food-web assembly. Through the simulation of various scenarios of plant and animal complementarity change, we sought to elucidate the mechanisms underlying the observed increases in (1) primary productivity, (2) control of herbivores by predators, and (3) reduction of herbivore pressure on plants in species-rich communities. 3. Our findings reveal that increased niche complementarity of plants can steepen the diversity-function relationships if it does not increase their intraspecific competition, while increasing complementarity among animals during community assembly can also have a positive effect but with considerable variability. 4. The study highlights the importance of trait variation both among and within species, and the interplay between intra- and interspecific competition strength in shaping the functioning of ecosystems over time. These results offer insights into the mechanisms underpinning the diversity-functioning relationship, and have practical implications for ecosystem management and conservation efforts.

On a global scale, fisheries harvest an estimated 96 million tonnes of fish biomass annually, making them one of the most important drivers of marine ecosystem biodiversity. Yet little is known about the interactions between fisheries and the dynamics of complex food webs in which the harvested species are embedded. We have developed a synthetic model that combines resource economics with complex food webs to examine the direct effects of fishing on exploited species and the indirect impact on other species in the same community. Our model analyses show that the sensitivity of the targeted species increases with its trophic level and decreases with its local interaction complexity (i.e. its number of interactions with prey, predators, and competitors). In addition, we also document a strikingly positive effect of community species richness on the resilience of the harvested species to this disturbance. The indirect effects on other species show specific patterns of spreading across trophic modules that differ systematically from how other disturbances spread across ecological networks. While these results call for further research on how human resource exploitation in general and fishery in particular affect ecological dynamics and biodiversity in naturally complex systems, they also allow for some cautious conclusions. Taken together, our results suggest that the sustainability concerning fishery yield and ecosystem integrity can be maximised by focusing the harvest on low trophic level species with a high local interaction complexity in high biodiversity ecosystems. In this sense, our complex network approach offers a promising avenue for integrating the necessities of generating economic revenue with the protection of natural biodiversity.

For over a decade, multiple studies have disputed the notion of natural killer (NK) cells as purely innate lymphocytes by demonstrating that they are capable of putative antigen-specific immunological memory against multiple infectious agents including two critical global health priorities – HIV and influenza. However, the mechanisms underlying antigen specificity remain unknown. Herein, we demonstrate that antigen-specific human NK cell memory develops upon exposure to both HIV and influenza, unified by a conserved and epitope-specific targetable mechanism firmly dependent on the activating CD94/NKG2C receptor and its ligand HLA-E, and confirm these findings by three rigorous and novel assays. We validated the permanent acquisition of antigen-specificity by individual memory NK cells by single-cell cloning. We identified biomarkers of antigen-specific NK cell memory through RNA-Seq transcriptomic fingerprints and complex immunophenotyping by 30-parameter flow cytometry showing elevated expression of KLRG1, α4β7 and NKG2C. Finally, we show individual HLA-E-restricted peptides that may constitute the dominant response in HIV-1- and influenza-infected persons in vivo. Our findings clarify the mechanisms behind formation of antigen-specific memory NK cells, and suggest they could be targeted for future vaccines, cure strategies, or other therapeutic interventions.

Human language enables us to externalise self-internal information (e.g. emotions or beliefs that are not readily accessible to others). Thus, language bridges the gap between the self and the other (e.g. Frith and Frith, 2010) in a way that possibly no other communication system can provide. In many languages, the difference between the self and others is directly reflected in the distinction between first (“I”), second (“you”) and third person (“he, she”) marking. In the present study, we compared ERPs to first, second and third person pronouns during the comprehension of an audio-book version of The Little Prince. Our results revealed a strong P300 response following first person pronouns that is independent of contextual factors. In line with previous research on self-relevance and the P300 (e.g. Knolle, Schröger, and Kotz, 2013b), our results suggest that first person marking is an attentional cue for self-relevance that is at the core of successful narrative comprehension. Refereed/Peer-reviewed

The free radical theory of aging is based on the idea that reactive oxygen species (ROS) may lead to the accumulation of age-related protein oxidation. Because themajority of cellular ROS is generated at the respiratory electron transport chain, this study focuses on the mitochondrial proteome of the aging model Podospora anserina as target for ROS-induced damage. To ensure the detection of even low abundant modified peptides, separation by long gradient nLC-ESI-MS/MS and an appropriate statistical workflow for iTRAQ quantification was developed. Artificial protein oxidation was minimized by establishing gel-free sample preparation in the presence of reducing and iron-chelating agents. This first large scale, oxidative modification-centric study for P. anserina allowed the comprehensive quantification of 22 different oxidative amino acid modifications, and notably the quantitative comparison of oxidized and nonoxidized protein species. In total 2341 proteins were quantified. For 746 both protein species (unmodified and oxidatively modified) were detected and the modification sites determined. The data revealed that methionine residues are preferably oxidized. Further prominent identified modifications in decreasing order of occurrence were carbonylation as well as formation of N-formylkynurenine and pyrrolidinone. Interestingly, for the majority of proteins a positive correlation of changes in protein amount and oxidative damage were noticed, and a general decrease in protein amounts at late age. However, it was discovered that few proteins changed in oxidative damage in accordance with former reports. Our data suggest that P. anserina is efficiently capable to counteract ROS-induced protein damage during aging as long as protein de novo synthesis is functioning, ultimately leading to an overall constant relationship between damaged and undamaged protein species. These findings contradict a massive increase in protein oxidation during aging and rather suggest a protein damage homeostasis mechanism even at late age.

Novel influenza vaccine approaches to achieve cross-protection against a broad range of antigenically distinct strains are needed. Beyond their ability to eliminate infected cells without the need for prior sensitization, natural killer (NK) cells have been shown to mediate virus-specific recall responses. Notably, exposure to influenza antigens induces protective influenza-specific memory NK cells in mice, but evidence of influenza-specific memory NK cells in humans is still lacking. Using intracellular cytokine staining, we found that NK cells from 45% of adults can robustly respond to nucleoprotein (NP) from at least 2 heterosubtypic influenza strains completely independent of T cell help. To further determine if a subset of NK cells can specifically react to NP peptide pools from distinct strains, we clonally expanded individual NK cells (NKCL) and measured H1N1, H2N2 and H3N2 NP-specific killing by 33 NKCL from 6 donors. 63% of NKCL showed positive responses against the 2009 H1N1 pandemic strain (2%–57% specific lysis). Strikingly, half of H1N1 NP-specific NKCL also displayed cytotoxicity against either H2N2 or H3N2 (9%–100% specific lysis) or against both H2N2 and H3N2 strains (5%–11% specific lysis). Potent killing by NKCLs was associated with high cell surface expression of the activating NKG2C receptor, a ligand for HLA-E. Accordingly, we identified an HLA-E-restricted NP epitope that triggers activation of influenza-specific NK cells. Collectively, these data provide the first mechanistic evidence of influenza-specific memory NK cells in humans and suggest influenza-specific responses mediated by NK cells may have the potential to be harnessed to enhance influenza vaccine-induced cross-protection.

Zusammenfassung Wenn eine Anaphylaxie auftritt, liegt ein allergologischer Notfall vor. Diese ist definiert durch das plotzliche Auftreten allergischer Symptome an zwei oder mehr Organsystemen. Aufgrund der Akuitat der Symptome und der potenziellen Lebensbedrohung fur den Patienten ergeben sich besondere Anforderungen an die medizinische Betreuung. Die Inzidenz der Anaphylaxie hat in den letzten Jahren zugenommen. Die haufigsten Ausloser der mastzellvermittelten und zumeist histaminabhangigen Anaphylaxie sind Nahrungsmittel, Insektengifte und Medikamente. Der Schweregrad einer Anaphylaxie wird nach Ring und Messmer in vier klinische Stadien eingeteilt, wobei im Stadium I ausschlieslich kutane Symptome auftreten, wahrend im Stadium IV eine Schocksituation mit Herzkreislauf- und/oder Atemstillstand einsetzt. Die adaquate Therapie der Anaphylaxie muss stadienorientiert erfolgen. Als medikamentose Erstmasnahme wird die intramuskulare Applikation von Adrenalin in die Oberschenkelauflenseite fur alle Reaktionen, die nicht nur Haut bzw. Schleimhaut, sondern auch das respiratorische und/oder das Herz-Kreislauf-System betreffen, empfohlen. Die weitere medikamentose Therapie beinhaltet die idealerweise intravenose Gabe von Antihistaminika und gewichtsadaptiert Kortikosteroiden, zur Selbstbehandlung im Notfall sollten die Praparate als Tabletten vorliegen. Summary Anaphylaxis is characterised by the sudden onset of acute allergic symptoms involving two or more organ systems. An acute allergic emergency is a challenge for physicians due to its life-threatening potential. The incidence of anaphylactic reactions has increased in recent years. Most frequent elicitors of mast cell and primarily histamine dependent anaphylactic reactions are food, insect venom or drugs. Allergic reactions are graded into four groups according to the classification by Ring and Messmer; grade I is defined by the onset of cutaneous symptoms only whereas grade IV is characterized by cardiovascular shock as well as cardiac and/or respiratory arrest. The treatment of allergic reactions should be guided by the severity of the reaction. Initially an intramuscular epinephrine injection into the lateral thigh should be given if cutaneous, mucosal and cardiovascular/respiratory symptoms occur. Additionally, the patient should receive intravenous antihistamines and corticosteroids. For self-treatment in the case of an allergic emergency, oral antihistamines and corticosteroids should be prescribed to the patient.

Anaphylaxis is characterized by the sudden onset of acute allergic symptoms involving two or more organ systems. An acute allergic emergency is a challenge for physicians due to its life-threatening potential. The incidence of anaphylactic reactions has increased in recent years. Most frequent elicitors of mast cell and primarily histamine dependent anaphylactic reactions are food, insect venom or drugs. Allergic -reactions are graded into four groups according to the classification by Ring and Messmer; grade I is defined by the onset of cutaneous symptoms only whereas grade IV is characterized by cardiovascular shock as well as cardiac and/or respiratory arrest. The treatment of allergic reactions should be guided by the severity of the reaction. Initially an intramuscular epinephrine injection into the lateral thigh should be given if cutaneous, mucosal and cardiovascular/respiratory symptoms occur. Additionally, the patient should receive intravenous antihistamines and corticosteroids. For self-treatment in the case of an allergic emergency, oral antihistamines and corticosteroids should be prescribed to the patient.

To elucidate the molecular basis of the link between respiration and longevity, we have studied the organization of the respiratory chain of a wild-type strain and of two long-lived mutants of the filamentous fungus Podospora anserina. This established aging model is able to respire by either the standard or the alternative pathway. In the latter pathway, electrons are directly transferred from ubiquinol to the alternative oxidase and thus bypass complexes III and IV. We show that the cytochrome c oxidase pathway is organized according to the mammalian “respirasome” model (Schagger, H., and Pfeiffer, K. (2000) EMBO J. 19, 1777–1783). In contrast, the alternative pathway is composed of distinct supercomplexes of complexes I and III (i.e. I2 and I2III2), which have not been described so far. Enzymatic analysis reveals distinct functional properties of complexes I and III belonging to either cytochrome c oxidase- or alternative oxidase-dependent pathways. By a gentle colorless-native PAGE, almost all of the ATP synthases from mitochondria respiring by either pathway were preserved in the dimeric state. Our data are of significance for the understanding of both respiratory pathways as well as lifespan control and aging.

P. anserina mutants with impairments in complex IV (COX) of the respiratory chain are characterized by an increase in lifespan. Examples are the nuclear grisea mutant with a moderate lifespan extension (60%) and the immortal extranuclear ex1 mutant. Here we report data demonstrating that in mutant ex1 the level of the alternative oxidase (PaAOX) is significantly higher than in mutant grisea. PaAOX levels appear to be reversely dependent on COX activity. The activity profile of superoxide dismutases in the ex1 mutant resembles the profile in senescent wild-type cultures with a high cytoplasmic copper/zinc superoxide dismutase (PaSOD1) and a low mitochondrial manganese superoxide dismutase (PaSOD2) activity. In the grisea mutant, PaSOD1 activity is only detectable in cultures grown in copper-supplemented medium. The two copper-regulated genes PaCtr3 (coding for a high affinity copper transporter) and PaSod2 are not expressed in the two mutants grown in standard medium. The repression of these genes as well as the activity of PaSOD1 is dependent on the availability of cellular copper, which appears to be high in COX-deficient strains such as mutant ex1 and in the senescent wild-type strain. In the wild-type, changes in the cellular localization of copper and in the delivery of this metal to different proteins appear to occur during senescence. Collectively, the data explain the characteristic lifespan of the investigated strains as the result of differences in energy transduction and in the machinery protecting against oxidative stress.

Background and aim Atopic dermatitis is often associated with atopic comorbidities such as allergic rhinitis, allergic asthma and food allergy. The aim of the present study was to analyze treatment data pertaining to atopic dermatitis patients in Germany with regard to the presence of other atopic comorbidities in the primary care and to investigate whether the presence of atopic codiagnoses has an impact on the treatment of atopic dermatitis (AD) patients. Methods We used data from the Disease Analyzer database (IMS HEALTH, Germany) including 1,631 physicians (general practitioners, dermatologists and pediatricians) and 3.3 million patients. 39,642 (7.5%) of these patients were treated by dermatologists, 17,124 (5.2%) by pediatricians and 15,774 (0.9%) by general practitioners and had a documented diagnosis of atopic dermatitis. Results 46.4% of AD patients treated by general practitioners, 42.5% by dermatologists and 32.0% by pediatricians were codiagnosed with one defined atopic diseases (allergic asthma, urticaria, allergic rhinitis and food allergy). In patients without AD, the proportion of atopic diseases was significantly smaller (41.4% for those treated by general practitioners, 38.4% for those treated by dermatologists, 26.4% for those treated by pediatricians). AD patients with another atopic comorbidity received topical corticosteroids (CS) (42.5%) more frequently than those without comorbidity (46.4% vs. 41.4% for patients treated by general practitioners, 42.5% vs. 38.4% for patients treated by dermatologists, 32.0% vs. 26.4% for patients treated by pediatricians). The general practitioners and pediatricians prescribed systemic corticosteroids to 13.2% and 7.8% of AD patients with additional atopic diseases, while the rate was only 5.1% and 3.0% in patients without comorbidities. Conclusion In AD patients, the share of patients diagnosed with atopic diseases is significantly higher than in patients without AD. AD outpatients with concomitant atopic comorbidities receive topical, but also systemic corticosteroid prescriptions more frequently.

We have previously shown that the control of cellular copper homeostasis by the copper-modulated transcription factor GRISEA has an important impact on the phenotype and lifespan of Podospora anserina. Here we demonstrate that copper depletion leads to the induction of an alternative respiratory pathway and to an increase in lifespan. This response compensates mitochondrial dysfunctions via the expression of PaAox, a nuclear gene coding for an alternative oxidase. It resembles the retrograde response in Saccharomyces cerevisiae. In P. anserina, this pathway appears to be induced by specific impairments of the copper-dependent cytochrome c oxidase. It is not induced as the result of a general decline of mitochondrial functions during senescence. We cloned and characterized PaAox. Transcript levels are decreased when cellular copper, superoxide, and hydrogen peroxide levels are raised. Copper also controls transcript levels of PaSod2, the gene encoding the mitochondrial manganese superoxide dismutase (PaSOD2). PaSod2 is a target of transcription factor GRISEA. During the senescence of wild-type strain s, the activity of PaSOD2 decreases, whereas the activity of the cytoplasmic copper/zinc superoxide dismutase (PaSOD1) increases. Collectively, the data explain the postponed senescence of mutant grisea as a defined consequence of copper depletion, ultimately leading to a reduction of oxidative stress. Moreover, they suggest that during senescence of the wild-type strain, copper is released from mitochondria. The involved mechanism is unknown. However, it is striking that the permeability of mitochondrial membranes in animal systems changes during apoptosis and that mitochondrial proteins with an important impact on this type of cellular death are released.

Aging of biological systems is controlled by various processes which have a potential impact on gene expression. Here we report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina. Total RNA of three individuals of defined age were pooled and analyzed by SuperSAGE (serial analysis of gene expression). A bioinformatics analysis identified different molecular pathways to be affected during aging. While the abundance of transcripts linked to ribosomes and to the proteasome quality control system were found to decrease during aging, those associated with autophagy increase, suggesting that autophagy may act as a compensatory quality control pathway. Transcript profiles associated with the energy metabolism including mitochondrial functions were identified to fluctuate during aging. Comparison of wild-type transcripts, which are continuously down-regulated during aging, with those down-regulated in the long-lived, copper-uptake mutant grisea, validated the relevance of age-related changes in cellular copper metabolism. Overall, we (i) present a unique age-related data set of a longitudinal study of the experimental aging model P. anserina which represents a reference resource for future investigations in a variety of organisms, (ii) suggest autophagy to be a key quality control pathway that becomes active once other pathways fail, and (iii) present testable predictions for subsequent experimental investigations.

The species name "Podospora anserina" is spelled incorrectly in the article title. The correct title is: "A Genome-Wide Longitudinal Transcriptome Analysis of the Aging Model Podospora anserina." The correct Citation is: Philipp O, Hamann A, Servos J, Werner A, Koch I, et al. (2013) A Genome-Wide Longitudinal Transcriptome Analysis of the Aging Model Podospora anserina. PLoS ONE 8(12): e83109. doi:10.1371/journal.pone.0083109

Anaphylaxis is characterized by the sudden onset of acute allergic symptoms involving two or more organ systems. An acute allergic emergency is a challenge for physicians due to its life-threatening potential. The incidence of anaphylactic reactions has increased in recent years. Most frequent elicitors of mast cell and primarily histamine dependent anaphylactic reactions are food, insect venom or drugs. Allergic -reactions are graded into four groups according to the classification by Ring and Messmer; grade I is defined by the onset of cutaneous symptoms only whereas grade IV is characterized by cardiovascular shock as well as cardiac and/or respiratory arrest. The treatment of allergic reactions should be guided by the severity of the reaction. Initially an intramuscular epinephrine injection into the lateral thigh should be given if cutaneous, mucosal and cardiovascular/respiratory symptoms occur. Additionally, the patient should receive intravenous antihistamines and corticosteroids. For self-treatment in the case of an allergic emergency, oral antihistamines and corticosteroids should be prescribed to the patient.

Item does not contain fulltext Many questions concerning the molecular processes during biological aging remain unanswered. Since mitochondria are central players in aging, we applied quantitative two-dimensional difference gel electrophoresis (2D-DIGE) coupled to protein identification by mass spectrometry to study the age-dependent changes in the mitochondrial proteome of the fungus Podospora anserina - a well-established aging model. 67 gel spots exhibited significant, but remarkably moderate intensity changes. While typically the observed changes in protein abundance occurred progressively with age, for several proteins a pronounced change was observed at late age, sometimes inverting the trend observed at younger age. The identified proteins were assigned to a wide range of metabolic pathways including several implicated previously in biological aging. An overall decrease for subunits of complexes I and V of oxidative phosphorylation was confirmed by Western blot analysis and blue-native electrophoresis. Changes in several groups of proteins suggested a general increase in protein biosynthesis possibly reflecting a compensatory mechanism for increased quality control-related protein degradation at later age. Age-related augmentation in abundance of proteins involved in biosynthesis, folding, and protein degradation pathways sustain these observations. Furthermore, a significant decrease of two enzymes involved in the degradation of gamma-aminobutyrate (GABA) supported its previously suggested involvement in biological aging. BIOLOGICAL SIGNIFICANCE: We have followed the time course of changes in protein abundance during aging of the fungus P. anserina. The observed moderate but significant changes provide insight into the molecular adaptations to biological aging and highlight the metabolic pathways involved, thereby offering new leads for future research.

A nucleotide stretch located upstream of the MRAS3 gene of the zygomycete Mucor racemosus was found to hybridize to multiple restriction fragments of genomic DNA of the ascomycete Podospora anserina . DNA of strains derived from different geographical locations revealed no major restriction length fragment polymorphisms. Also, no age-related polymorphisms were observed. The repetitive sequence is located on all of the physically fractionated Podospora chromosomes. Sequence analysis of the upstream sequence of MRAS3 and of a DNA-stretch from a genomic clone of P. anserina which hybridized to the Mucor probe revealed a region of sequence homology. This sequence is composed of alternating G and T residues [poly(dG-dT) or poly(GT)] of 76 bp in length and thus represents a simple repetitive sequence, or microsatellite. A synthetic oligonucleotide, (GT) 8 , corresponding to this sequence gave also rise to a complex hybridization pattern. Screening of genomic libraries of P. anserina revealed poly(GT)-stretches on about 5–7% of all clones. Finally, this repetitive sequence was identified in the genome of the filamentous fungi Sordaria macrospora and Curvularia lunata .

The possibility of using MOODLE e-learning platform as an environment for education of database issues, concerning basic database objects and users creating, analysis and transaction management was analyzed in the paper. All of needed extensions were made using php scripts and were tested in the chosen database servers: MySQL, SQL Server and Oracle DBMS. Results of these tests were satisfactory, confirming preliminary assumptions for using e-learning MOODLE platform in the interactive teaching of database issues.

Udgivelsesdato: 2009-Aug The free radical theory of ageing states that ROS play a key role in age-related decrease in mitochondrial function via the damage of mitochondrial DNA (mtDNA), proteins and lipids. In the sexually reproducing ascomycete Podospora anserina ageing is, as in other eukaryotes, associated with mtDNA instability and mitochondrial dysfunction. Part of the mtDNA instabilities may arise due to accumulation of ROS induced mtDNA lesions, which, as previously suggested for mammals, may be caused by an age-related decrease in base excision repair (BER). Alignments of known BER protein sequences with the P. anserina genome revealed high homology. We report for the first time the presence of BER activities in P. anserina mitochondrial extracts. DNA glycosylase activities decrease with age, suggesting that the increased mtDNA instability with age may be caused by decreased ability to repair mtDNA damage and hence contribute to ageing and lifespan control in this ageing model. Additionally, we find low DNA glycosylase activities in the long-lived mutants grisea and DeltaPaCox17::ble, which are characterized by low mitochondrial ROS generation. Overall, our data identify a potential role of mtDNA repair in controlling ageing and life span in P. anserina, a mechanism possibly regulated in response to ROS levels.

Recent biochemical evidence has indicated the existence of respiratory supercomplexes as well as ATP synthase oligomers in the inner mitochondrial membrane of different eukaryotes. We have studied the organization of the respiratory chain of a wild-type strain and of two long-lived mutants of the filamentous fungus Podospora anserina. This aging model is able to respire by either the standard or the alternative pathway. In the latter, electrons are directly transferred from ubiquinol to the alternative oxidase (AOX) and thus bypass complexes III and IV. We showed that the two pathways are composed of distinct respiratory supercomplexes. These data are of significance for the understanding of both respiratory pathways as well as of life-span control and aging.

Deletion of genes in Podospora anserina via conventional methods is an inefficient and time-consuming process since homologous recombination occurs normally only at low frequency (about 1%). To improve the efficiency of replacement, we adopted the two-step protocol developed for Aspergillus nidulans (Chaveroche et al. in Nucleic Acids Res 28:E97, 2000). As a prerequisite, a vector was generated containing a blasticidin resistance cassette for selection in the Escherichia coli host strain KS272 (pKOBEG) and a phleomycin resistance cassette for selection in P. anserina. A derivative of this vector, into which short ( approximately 250 bp) PCR-generated sequences flanking the gene to be deleted have been integrated, is introduced into the E. coli host strain which contains a cosmid with the gene of interest and long 5' and 3' flanking sequences. Subsequently, a cosmid is reisolated from E. coli in which the gene of interest is replaced by the resistance cassette. This construct is used to transform P. anserina. The long stretches flanking the resistance cassette facilitate recombination with homologous sequences in the fungal genome and increase the efficiency of gene deletion up to 100%. The procedure is not dependent on the availability of specific auxotrophic mutant strains and may be applicable to other fungi.

P. anserina mutants with impairments in complex IV (COX) of the respiratory chain are characterized by an increase in lifespan. Examples are the nuclear grisea mutant with a moderate lifespan extension (60%) and the immortal extranuclear ex1 mutant. Here we report data demonstrating that in mutant ex1 the level of the alternative oxidase (PaAOX) is significantly higher than in mutant grisea. PaAOX levels appear to be reversely dependent on COX activity. The activity profile of superoxide dismutases in the ex1 mutant resembles the profile in senescent wild-type cultures with a high cytoplasmic copper/zinc superoxide dismutase (PaSOD1) and a low mitochondrial manganese superoxide dismutase (PaSOD2) activity. In the grisea mutant, PaSOD1 activity is only detectable in cultures grown in copper-supplemented medium. The two copper-regulated genes PaCtr3 (coding for a high affinity copper transporter) and PaSod2 are not expressed in the two mutants grown in standard medium. The repression of these genes as well as the activity of PaSOD1 is dependent on the availability of cellular copper, which appears to be high in COX-deficient strains such as mutant ex1 and in the senescent wild-type strain. In the wild-type, changes in the cellular localization of copper and in the delivery of this metal to different proteins appear to occur during senescence. Collectively, the data explain the characteristic lifespan of the investigated strains as the result of differences in energy transduction and in the machinery protecting against oxidative stress.

The release of reactive oxygen species (ROS) as side products of aerobic metabolism in the mitochondria is an unavoidable consequence. As the capacity of organisms to deal with this exposure declines with age, accumulation of molecular damage caused by ROS has been defined as one of the central events during the ageing process in biological systems as well as in numerous diseases such as Alzheimer's and Parkinson's Dementia.In the filamentous fungus Podospora anserina, an ageing model with a clear defined mitochondrial etiology of ageing, in addition to the mitochondrial aconitase the ATP synthase alpha subunit was defined recently as a hot spot for oxidative modifications induced by ROS. In this report we show, that this reactivity is not randomly distributed over the ATP Synthase, but is channeled to a single tryptophan residue 503. This residue serves as an intra-molecular quencher for oxidative species and might also be involved in the metabolic perception of oxidative stress or regulation of enzyme activity. A putative metal binding site in the proximity of this tryptophan residue appears to be crucial for the molecular mechanism for the selective targeting of oxidative damage.