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Summary Siderophores are organic compounds with low molecular masses that are produced by microorganisms and plants growing under low iron conditions. The primary function of these compounds is to chelate the ferric iron [Fe(III)] from different terrestrial and aquatic habitats and thereby make it available for microbial and plant cells. Siderophores have received much attention in recent years because of their potential roles and applications in various areas of environmental research. Their significance in these applications is because siderophores have the ability to bind a variety of metals in addition to iron, and they have a wide range of chemical structures and specific properties. For instance, siderophores function as biocontrols, biosensors, and bioremediation and chelation agents, in addition to their important role in weathering soil minerals and enhancing plant growth. The aim of this literature review is to outline and discuss the important roles and functions of siderophores in different environmental habitats and emphasize the significant roles that these small organic molecules could play in applied environmental processes. The paper outlines the different types of siderophores. Also it discusses the important roles and functions of siderophores in different environmental habitats.

Key Points Oxidants, such as hydrogen peroxide and superoxide anions, can damage cellular components when produced in large amounts. When reactive oxygen species (ROS) are produced at lower, regulated levels, they can function in a diverse array of signalling pathways. Members of the NADPH oxidase (NOX) family are important generators of intracellular ROS and have an important role in reduction–oxidation (redox) signalling. Most redox signalling occurs by the reversible oxidation and reduction of crucial reactive Cys residues. One example is the family of protein Tyr phosphatases, which can be transiently inactivated by oxidation of the catalytic Cys residue. Although it is less well understood than NOX-generated ROS, mitochondrial ROS production seems to be regulated in some manner and can also modulate signalling pathways. Oxidant signalling might be an ancient mode of signal transduction, as it is observed in both plants and animals. Increasing evidence indicates that redox signalling might have a crucial role in the immune response, stem cell biology, cancer and ageing. Although they are damaging when produced in large quantities, low levels of reactive oxygen species (ROS) can function within specific signalling pathways, based on the reversible oxidation of crucial Cys residues in reduction–oxidation (redox)-sensitive target proteins. Understanding these pathways has implications for metabolic regulation, innate immunity, stem cell biology, tumorigenesis and ageing. Reactive oxygen species (ROS), which were originally characterized in terms of their harmful effects on cells and invading microorganisms, are increasingly implicated in various cell fate decisions and signal transduction pathways. The mechanism involved in ROS-dependent signalling involves the reversible oxidation and reduction of specific amino acids, with crucial reactive Cys residues being the most frequent target. In this Review, we discuss the sources of ROS within cells and what is known regarding how intracellular oxidant levels are regulated. We further discuss the recent observations that reduction–oxidation (redox)-dependent regulation has a crucial role in an ever-widening range of biological activities — from immune function to stem cell self-renewal, and from tumorigenesis to ageing.

The E3 ubiquitin ligase Parkin mediates the clearance of depolarized mitochondria through the autophagy pathway. PINK1 kinase activity is required for Parkin translocation to depolarized mitochondria where Parkin generates polyubiquitin chains on the voltage-dependent anion channel (VDAC1) to recruit the autophagic adaptor p62/SQSTM1. Parkinson's disease is the most common neurodegenerative movement disorder. Mutations in PINK1 and PARKIN are the most frequent causes of recessive Parkinson's disease. However, their molecular contribution to pathogenesis remains unclear. Here, we reveal important mechanistic steps of a PINK1/Parkin-directed pathway linking mitochondrial damage, ubiquitylation and autophagy in non-neuronal and neuronal cells. PINK1 kinase activity and its mitochondrial localization sequence are prerequisites to induce translocation of the E3 ligase Parkin to depolarized mitochondria. Subsequently, Parkin mediates the formation of two distinct poly-ubiquitin chains, linked through Lys 63 and Lys 27. In addition, the autophagic adaptor p62/SQSTM1 is recruited to mitochondrial clusters and is essential for the clearance of mitochondria. Strikingly, we identified VDAC1 (voltage-dependent anion channel 1) as a target for Parkin-mediated Lys 27 poly-ubiquitylation and mitophagy. Moreover, pathogenic Parkin mutations interfere with distinct steps of mitochondrial translocation, ubiquitylation and/or final clearance through mitophagy. Thus, our data provide functional links between PINK1, Parkin and the selective autophagy of mitochondria, which is implicated in the pathogenesis of Parkinson's disease.

The calreticulin (CALR) exon 9 mutations are found in ∼30% of patients with essential thrombocythemia and primary myelofibrosis. Recently, we reported spontaneous immune responses against the CALR mutations. Here, we describe that CALR-mutant (CALRmut)-specific T cells are able to specifically recognize CALRmut cells. First, we established a T-cell culture specific for a CALRmut epitope. These specific T cells were able to recognize several epitopes in the CALRmut C terminus. Next, we established a CALRmut-specific CD4+ T-cell clone by limiting dilution. These CD4+ T cells recognized autologous CALRmut monocytes and hematopoietic stem cells, and T-cell recognition of target cells was dependent on the presence of CALR. Furthermore, we showed that the CALRmut response was human leukocyte antigen (HLA)-DR restricted. Finally, we demonstrated that the CALRmut-specific CD4+ T cells, despite their phenotype, were cytotoxic to autologous CALRmut cells, and that the cytotoxicity was mediated by degranulation of the T cells. In conclusion, the CALR exon 9 mutations are targets for specific T cells and thus are promising targets for cancer immune therapy such as peptide vaccination in patients harboring CALR exon 9 mutations.

Transcription factor Nrf2 and its repressor Keap1 regulate a network of cytoprotective genes involving more than 1% of the genome, their best known targets being drug-metabolizing and antioxidant genes. Here we demonstrate a novel role for this pathway in directly regulating mitochondrial bioenergetics in murine neurons and embryonic fibroblasts. Loss of Nrf2 leads to mitochondrial depolarisation, decreased ATP levels and impaired respiration, whereas genetic activation of Nrf2 increases the mitochondrial membrane potential and ATP levels, the rate of respiration and the efficiency of oxidative phosphorylation. We further show that Nrf2-deficient cells have increased production of ATP in glycolysis, which is then used by the F1Fo-ATPase for maintenance of the mitochondrial membrane potential. While the levels and in vitro activities of the respiratory complexes are unaffected by Nrf2 deletion, their activities in isolated mitochondria and intact live cells are substantially impaired. In addition, the rate of regeneration of NADH after inhibition of respiration is much slower in Nrf2-knockout cells than in their wild-type counterparts. Taken together, these results show that Nrf2 directly regulates cellular energy metabolism through modulating the availability of substrates for mitochondrial respiration. Our findings highlight the importance of efficient energy metabolism in Nrf2-mediated cytoprotection.

Hydrogen at speed The extrasolar planet HD 209458b is surrounded by a vast cloud of atomic hydrogen, covering a region larger than the stellar disk. A spectral line observed when the planet passed in front of its host star revealed the presence of high-velocity atomic hydrogen a great distance away from the planet, and this was interpreted as hydrogen atoms escaping from the planet's exosphere and being accelerated by stellar radiation pressure. Starting from the fact that energetic neutral atoms are seen in the Solar System wherever energetic ions from the solar wind encounter a neutral planetary atmosphere, Holmström et al . have developed an alternative model. In this, stellar wind particles pick up electrons from neutral hydrogen in the planet's exosphere to generate energetic neutral atoms. The extrasolar planet HD 209458b has high-velocity atomic hydrogen at great distances from it; this observation can be explained by stellar wind particles picking up electrons from neutral hydrogen in the planet's exosphere. Absorption in the stellar Lyman-α (Lyα) line observed during the transit of the extrasolar planet HD 209458b in front of its host star reveals high-velocity atomic hydrogen at great distances from the planet 1 , 2 . This has been interpreted as hydrogen atoms escaping from the planet’s exosphere 1 , 3 , possibly undergoing hydrodynamic blow-off 4 , and being accelerated by stellar radiation pressure. Energetic neutral atoms around Solar System planets have been observed to form from charge exchange between solar wind protons and neutral hydrogen from the planetary exospheres 5 , 6 , 7 , however, and this process also should occur around extrasolar planets. Here we show that the measured transit-associated Lyα absorption can be explained by the interaction between the exosphere of HD 209458b and the stellar wind, and that radiation pressure alone cannot explain the observations. As the stellar wind protons are the source of the observed energetic neutral atoms, this provides a way of probing stellar wind conditions, and our model suggests a slow and hot stellar wind near HD 209458b at the time of the observations.

Heavy metal-contaminated soil derived from a former uranium mining site in Ronneburg, Germany, was used for sterile mesocosms inoculated with the extremely metal-resistant Streptomyces mirabilis P16B-1 or the sensitive control strain Streptomyces lividans TK24. The production and fate of bacterial hydroxamate siderophores in soil was analyzed, and the presence of ferrioxamines E, B, D, and G was shown. While total ferrioxamine concentrations decreased in water-treated controls after 30 days of incubation, the sustained production by the bacteria was seen. For the individual molecules, alteration between neutral and cationic forms and linearization of hydroxamates was observed for the first time. Mesocosms inoculated with biomass of either strain showed changes of siderophore contents compared with the non-treated control indicating for auto-alteration and consumption, respectively, depending on the vital bacteria present. Heat stability and structural consistency of siderophores obtained from sterile culture filtrate were shown. In addition, low recovery (32 %) from soil was shown, indicating adsorption to soil particles or soil organic matter. Fate and behavior of hydroxamate siderophores in metal-contaminated soils may affect soil properties as well as conditions for its inhabiting (micro)organisms.

Glutamate excitotoxicity is responsible for neuronal death in acute neurological disorders including stroke, trauma and neurodegenerative disease. Loss of calcium homeostasis is a key mediator of glutamate-induced cell death. The neurotransmitter dopamine (DA) is known to modulate calcium signalling, and here we show that it can do so in response to physiological concentrations of glutamate. Furthermore, DA is able to protect neurons from glutamate-induced cell death at pathological concentrations of glutamate. We demonstrate that DA has a novel role in preventing delayed calcium deregulation in cortical, hippocampal and midbrain neurons. The effect of DA in abolishing glutamate excitotoxicity can be induced by DA receptor agonists, and is abolished by DA receptor antagonists. Our data indicate that the modulation of glutamate excitotoxicity by DA is receptor-mediated. We postulate that DA has a major physiological function as a safety catch to restrict the glutamate-induced calcium signal, and thereby prevent glutamate-induced cell death in the brain.