Catálogo de publicaciones - libros

Copper ions play critical roles as electron transfer intermediates in various redox reactions. The yeast Saccharomyces cerevisiae has served as a valuable model to study copper metabolism in eukaryotic cells. The systems for copper homeostasis; including the uptake, cytoplasmic trafficking, and metabolism in intracellular organelles, detoxification, and regulation of these systems have been characterized. Most of the molecular components for copper metabolism identified in yeast are functionally and structurally conserved in mammals. These findings have underscored the importance of evolving delicate mechanisms to utilize copper. Studies on copper metabolism in yeast certainly have opened up interesting and important research avenues that have shed light on the molecular details of copper metabolism and the physiological roles of copper.

The first eukaryotic zinc uptake transporter was discovered in the yeast, Saccharomyces cerevisiae . Since then, this organism has been an invaluable tool for the discovery of genes involved in zinc homeostasis. Genomic and proteomic studies have revealed an abundance of Zn^2+-regulated genes and Zn^2+-binding proteins. The large number of essential functions of Zn^2+ necessitates a complex homeostatic mechanism involving the transport and storage of Zn^2+ as well as its allocation to essential sites. Studies in yeast have elucidated the opposing roles of the ZIP and CDF Zn^2+ transporter families and uncovered additional transport systems. The transcription factor, Zap1p, functions as the central Zn^2+ sensor by regulating genes involved in Zn^2+ uptake and adaptation to Zn^2+-deficiency. The investigation of the role of Zn^2+ in the regulation of signaling pathways is becoming a primary research direction, and yeast will undoubtedly play a major role in any discoveries in this field as well.

Iron homeostasis results from matching iron uptake to cell growth and division in the context of the overall cell requirement for iron. Fungi achieve this balance by transcriptional regulation of the genes that encode iron uptake activities; post-transcriptional regulation of the synthesis of proteins that use iron; and storage and recycling of iron to meet short-term needs in times of iron deprivation. In the Fungal Kingdom, both repression and activation mechanisms of transcriptional regulation have been elucidated; both mechanisms rely on transcription factors that directly or indirectly are regulated by cell iron status. Among fungi, however, one or the other transcriptional regulatory mechanism is used by a given organism but not both. In contrast, of those fungi examined in detail, all employ at least two of the four iron uptake mechanisms characterized in fungi in general: siderophore iron uptake; direct ferrous iron permeation; coupled ferroxidase/permease uptake; and heme/hemin uptake. All of these pathways rely on the activity of a metalloreductase enzyme at some point. The yeast vacuole serves as iron store while the mitochondrion, as the site of heme and Fe-S cluster biosynthesis, is the primary end-user of cell iron. The recycling of iron from both organelles plays a role in the maintenance of homeostasis both in terms of iron utilization and regulation of iron uptake.

The ability of mammals to tightly regulate systemic copper levels is vital for health as demonstrated by the severity of the genetic copper deficiency and copper toxicity disorders, Menkes disease and Wilson disease, respectively. Analysis of these genetic disorders has led to a substantial increase in the understanding of the role of copper in health and disease. The isolation of the genes involved in these diseases and use of yeast mutants with altered copper and iron homeostasis has revealed a range of molecular mechanisms governing copper homeostasis. These mechanisms include regulation of cellular copper uptake and efflux and involve the use of chaperones for safe intracellular copper distribution. Here we provide an overview of the physiological role of copper and the molecular mechanisms regulating systemic and cellular copper levels in mammals. Furthermore, we discuss the pathophysiological mechanisms and consequences of copper deficiency/overload in relation to disease.

Zinc is essential for cell proliferation thereby promoting growth and development, yet a rise of intracellular zinc is a leading cause of neuronal cell death in excitotoxic syndromes. While pervious studies have addressed mostly the structural role of zinc as a cofactor of numerous enzymes and zinc finger proteins, recent data suggest that zinc is acting as a signaling molecule. Despite the accumulating knowledge on the transporters, which are shown to maintain cellular and sub-cellular zinc homeostasis, the mechanisms by which they function are much less understood. Changes in extracellular or intracellular zinc trigger the activation of major signaling pathways, partially mediated by a specific zinc sensing receptor, which are linked to either cell growth or cell death. These proteins, which are regulated by zinc, will be the subject of this review. The major challenges in future studies will be to reveal the cellular network of zinc signaling and their links to cellular zinc homeostasis.

The uptake of iron into the body is tightly regulated in humans and in other mammals. Mutations in key proteins that transport, sense, metabolize, and facilitate the utilization of iron cause perturbations in iron homeostasis that result in iron deficiency or overload diseases. This review focuses on what is currently known about these diseases and the normal function of the proteins that are mutated in the disease-state. The proteins causing hereditary hemochromatosis and anemia are discussed in detail.

Plants depend upon iron for their growth and development. However, availability of this metal is low in soils, because of its insolubility at basic pH in presence of oxygen. Plants have, therefore, evolved various mechanisms to actively acquire iron from the soil, based either on reducing or chelating strategies. The molecular characterization of these uptake systems and the regulation of their synthesis have been widely documented the last few years. Distribution of iron to the various parts of a plant, and its compartmentation in various subcellular organelles is also described, but the molecular determinants required for these functions are yet poorly documented. Beside transport activities to establish iron homeostasis in plants, storage is also an important parameter. Part of this function is achieved by ferritins. These iron storage proteins are located within the plastids in plants, and regulated by iron at a transcriptional level.

Nutritional micronutrient deficiencies and exposure to pollutant metals threaten human health globally. Plant crops are at the beginning of a food chain that largely determines food metal contents. In order to survive, all organisms have to supply appropriate amounts of each micronutrient to the correct target apometalloproteins and at the same time avoid adventitious metal binding to non-target metal binding sites or other cellular compounds. This requires the operation of metal homeostasis networks, which orchestrate the mobilization, uptake, distribution, intracellular trafficking, chelation, and sequestration of all metal ions. Presumably as a result of time-dependent and local variations in bioavailable soil metal concentrations, plant metal homeostasis networks exhibit a remarkably high degree of plasticity and natural diversity. This is a review covering the current knowledge of metal-dependent processes and proteins, metal homeostasis and its regulation, and the molecular mechanisms underlying naturally selected metal hypertolerance and metal hyperaccumulation in higher plants.

Metal immobilization away from metabolically active sites within the cell represents the last step in both the homeostasis of metals and the detoxification of metal in excess. Assessment of the importance of this step requires having access to the in vivo speciation of metals. Evolving techniques have made it possible to acquire more reliable in situ profiling of: (i) spatio-temporal accumulation of metal, (ii) characterization of the metal-ligands complexes and determination of the structure of the different bio-ligands involved. The chapter ”metal immobilization: where and how?” presents the role of different metal-chelators in plants, based on examples from works using non-invasive techniques and genetic approaches at both the whole plant, cellular and subcellular levels. The aim of the chapter is to give a survey of the key molecules and processes involved in metal immobilization in plants, on the basis of direct and robust evidences of the in vivo speciation of metals.

Phytoremediation is a group of technologies that use plants to reduce, remove, degrade, or immobilize environmental toxins, primarily those of anthropogenic origin, with the aim of restoring area sites to a condition useable for private or public applications. Phytoremediation efforts have largely focused on the use of plants to accelerate degradation of organic contaminants, usually in concert with root rhizosphere microorganisms, or remove hazardous heavy metals from soils or water. Phytoremediation of contaminated sites is a relatively inexpensive and aesthetically pleasing to the public compared to alternate remediation strategies involving excavation/removal or chemical in situ stabilization/conversion. Many phytoremediation plans have multi-year timetables, but since most sites in need of remediatrion have been contaminated for more than ten years, as such a ten year remediation plan does not seem excessive. Seven aspects of phytoremediation are described in this chapter: phytoextraction, phytodegradation, rhizosphere degradation, rhizofiltration, phytostabilization, phytovolatization, and phytorestoration. Combining technologies offer the greatest potential to efficiently phytoremediate contaminated sites. The major focus of this chapter is phytoextraction of arsenic, cadmium, chromium, copper, mercury, nickel, lead, selenium, and zinc.