Xiang Ming Xu

AtSufE is an essential activator of plastidic and mitochondrial desulfurases in Arabidopsis

Iron–sulfur (Fe–S) clusters are vital prosthetic groups for Fe–S proteins involved in fundamental processes such as electron transfer, metabolism, sensing and signaling. In plants, sulfur (SUF) protein‐mediated Fe–S cluster biogenesis involves iron acquisition and sulfur mobilization, processes suggested to be plastidic. Here we have shown that AtSufE in Arabidopsis rescues growth defects in SufE‐deficient Escherichia coli. In contrast to other SUF proteins, AtSufE localizes to plastids and mitochondria interacting with the plastidic AtSufS and mitochondrial AtNifS1 cysteine desulfurases. AtSufE activates AtSufS and AtNifS1 cysteine desulfurization, and AtSufE activity restoration in either plastids or mitochondria is not sufficient to rescue embryo lethality in AtSufE loss‐of‐function mutants. AtSufE overexpression induces AtSufS and AtNifS1 expression, which in turn leads to elevated cysteine desulfurization activity, chlorosis and retarded development. Our data demonstrate that plastidic and mitochondrial Fe–S cluster biogenesis shares a common, essential component, and that AtSufE acts as an activator of plastidic and mitochondrial desulfurases in Arabidopsis.

The Arabidopsis DJ-1a protein confers stress protection through cytosolic SOD activation

Mutations in the DJ-1 gene (also known as PARK7) cause inherited Parkinsons disease, which is characterized by neuronal death. Although DJ-1 is thought to be an antioxidant protein, the underlying mechanism by which loss of DJ-1 function contributes to cell death is unclear. Human DJ-1 and its Arabidopsis thaliana homologue, AtDJ-1a, are evolutionarily conserved proteins, indicating a universal function. To gain further knowledge of the molecular features associated with DJ-1 dysfunction, we have characterized AtDJ-1a. We show that AtDJ-1a levels are responsive to stress treatment and that AtDJ-1a loss of function results in accelerated cell death in aging plants. By contrast, transgenic plants with elevated AtDJ-1a levels have increased protection against environmental stress conditions, such as strong light, H2O2, methyl viologen and copper sulfate. We further identify superoxide dismutase 1 (SOD1) and glutathione peroxidase 2 (GPX2) as interaction partners of both AtDJ-1a and human DJ-1, and show that this interaction results in AtDJ-1a- and DJ-1-mediated cytosolic SOD1 activation in a copper-dependent fashion. Our data have highlighted a conserved molecular mechanism for DJ-1 and revealed a new protein player in the oxidative stress response of plants.

Iron–Sulfur Clusters: Biogenesis, Molecular Mechanisms, and Their Functional Significance

Iron-sulfur clusters [Fe-S] are small, ubiquitous inorganic cofactors representing one of the earliest catalysts during biomolecule evolution and are involved in fundamental biological reactions, including regulation of enzyme activity, mitochondrial respiration, ribosome biogenesis, cofactor biogenesis, gene expression regulation, and nucleotide metabolism. Although simple in structure, [Fe-S] biogenesis requires complex protein machineries and pathways for assembly. [Fe-S] are assembled from cysteine-derived sulfur and iron onto scaffold proteins followed by transfer to recipient apoproteins. Several predominant iron-sulfur biogenesis systems have been identified, including nitrogen fixation (NIF), sulfur utilization factor (SUF), iron-sulfur cluster (ISC), and cytosolic iron-sulfur protein assembly (CIA), and many protein components have been identified and characterized. In eukaryotes ISC is mainly localized to mitochondria, cytosolic iron-sulfur protein assembly to the cytosol, whereas plant sulfur utilization factor is localized mainly to plastids. Because of this spatial separation, evidence suggests cross-talk mediated by organelle export machineries and dual targeting mechanisms. Although research efforts in understanding iron-sulfur biogenesis has been centered on bacteria, yeast, and plants, recent efforts have implicated inappropriate [Fe-S] biogenesis to underlie many human diseases. In this review we detail our current understanding of [Fe-S] biogenesis across species boundaries highlighting evolutionary conservation and divergence and assembling our knowledge into a cellular context.

Iron–Sulfur Cluster Biogenesis Systems and their Crosstalk

The biogenesis of iron–sulfur clusters ([FeS]) plays a very important role in many essential functions of life. Several [FeS] biogenesis systems have been discovered, such as the NIF (nitrogen fixation), SUF (mobilisation of sulfur) and ISC (iron–sulfur cluster) systems in bacteria, and the ISC‐like and CIA (cytosolic iron–sulfur protein assembly) systems in yeast. Experimental evidence has revealed that SUF and ISC in bacteria communicate with each other partly through IscR to coordinate the utilisation of iron and cysteine. The ISC‐like system in yeast is localised to the mitochondria, while the ISC‐dependent CIA system is localised to the cytosol; this suggests a possible role for the ISC mitochondrial export machinery in mediating crosstalk between the two systems. Based on genetic analysis, the model plant Arabidopsis thaliana contains three [FeS] biogenesis systems similar to SUF, ISC and CIA named AtSUF, AtISC and AtCIA. Possible communication between these three systems has been proposed.

ROS removal by DJ-1: Arabidopsis as a new model to understand Parkinson's Disease.

Reactive oxygen species represent one of the principal factors that cause cell death and scavenging of reactive oxygen species by superoxide dismutase-related pathway is essential for cell survival. The Parkinson’s Disease-related DJ-1 protein (also known as PARK7) has been implicated in resistance against oxidative stress in dopaminergic neurons however, its molecular mechanism has to date been unknown. We have used Arabidopsis thaliana as a model system to demonstrate that DJ-1, in both plant and mammalian cells, directly influence SOD activity in a highly conserved manner thereby preventing cell death. These data not only provides evidence for the molecular mechanisms associated with DJ-1-induced Parkinson’s Disease but also highlight the unprecedented value of plants as a tool in understanding human disease mechanisms.

A Basic Set of Homeostatic Controller Motifs

Adaptation and homeostasis are essential properties of all living systems. However, our knowledge about the reaction kinetic mechanisms leading to robust homeostatic behavior in the presence of environmental perturbations is still poor. Here, we describe, and provide physiological examples of, a set of two-component controller motifs that show robust homeostasis. This basic set of controller motifs, which can be considered as complete, divides into two operational work modes, termed as inflow and outflow control. We show how controller combinations within a cell can integrate uptake and metabolization of a homeostatic controlled species and how pathways can be activated and lead to the formation of alternative products, as observed, for example, in the change of fermentation products by microorganisms when the supply of the carbon source is altered. The antagonistic character of hormonal control systems can be understood by a combination of inflow and outflow controllers.

Dual Localized AtHscB Involved in Iron Sulfur Protein Biogenesis in Arabidopsis

Background Iron-sulfur clusters are ubiquitous structures which act as prosthetic groups for numerous proteins involved in several fundamental biological processes including respiration and photosynthesis. Although simple in structure both the assembly and insertion of clusters into apoproteins requires complex biochemical pathways involving a diverse set of proteins. In yeast, the J-type chaperone Jac1 plays a key role in the biogenesis of iron sulfur clusters in mitochondria. Methodology/Principal Findings In this study we demonstrate that AtHscB from Arabidopsis can rescue the Jac1 yeast knockout mutant suggesting a role for AtHscB in iron sulfur protein biogenesis in plants. In contrast to mitochondrial Jac1, AtHscB localizes to both mitochondria and the cytosol. AtHscB interacts with AtIscU1, an Isu-like scaffold protein involved in iron-sulfur cluster biogenesis, and through this interaction AtIscU1 is most probably retained in the cytosol. The chaperone AtHscA can functionally complement the yeast Ssq1knockout mutant and its ATPase activity is enhanced by AtHscB and AtIscU1. Interestingly, AtHscA is also localized in both mitochondria and the cytosol. Furthermore, AtHscB is highly expressed in anthers and trichomes and an AtHscB T-DNA insertion mutant shows reduced seed set, a waxless phenotype and inappropriate trichome development as well as dramatically reduced activities of the iron-sulfur enzymes aconitase and succinate dehydrogenase. Conclusions Our data suggest that AtHscB together with AtHscA and AtIscU1 plays an important role in the biogenesis of iron-sulfur proteins in both mitochondria and the cytosol.

The value of Arabidopsis research in understanding human disease states.

Although Arabidopsis thaliana is traditionally viewed as the key model organism for plant biology it is becoming increasingly clear that Arabidopsis represents an invaluable tool in our efforts to understand molecular mechanisms that underpin human disease states. A comparison of the annotated Arabidopsis thaliana and human genome sequences reveals that a high percentage of genes implicated in human diseases are also present in Arabidopsis. Although Arabidopsis and humans diverged 1.6 billion years ago recent studies have demonstrated remarkable conservation of protein function and cellular processes between these seemingly distant species. In particular, cellular processes associated with neurodegenerative disorders, such as Alzheimers and Parkinsons disease, and the neurological disorder Friedreich Ataxia have been dissected using Arabidopsis.

The Organization of Controller Motifs Leading to Robust Plant Iron Homeostasis.

Iron is an essential element needed by all organisms for growth and development. Because iron becomes toxic at higher concentrations iron is under homeostatic control. Plants face also the problem that iron in the soil is tightly bound to oxygen and difficult to access. Plants have therefore developed special mechanisms for iron uptake and regulation. During the last years key components of plant iron regulation have been identified. How these components integrate and maintain robust iron homeostasis is presently not well understood. Here we use a computational approach to identify mechanisms for robust iron homeostasis in non-graminaceous plants. In comparison with experimental results certain control arrangements can be eliminated, among them that iron homeostasis is solely based on an iron-dependent degradation of the transporter IRT1. Recent IRT1 overexpression experiments suggested that IRT1-degradation is iron-independent. This suggestion appears to be misleading. We show that iron signaling pathways under IRT1 overexpression conditions become saturated, leading to a breakdown in iron regulation and to the observed iron-independent degradation of IRT1. A model, which complies with experimental data places the regulation of cytosolic iron at the transcript level of the transcription factor FIT. Including the experimental observation that FIT induces inhibition of IRT1 turnover we found a significant improvement in the system’s response time, suggesting a functional role for the FIT-mediated inhibition of IRT1 degradation. By combining iron uptake with storage and remobilization mechanisms a model is obtained which in a concerted manner integrates iron uptake, storage and remobilization. In agreement with experiments the model does not store iron during its high-affinity uptake. As an iron biofortification approach we discuss the possibility how iron can be accumulated even during high-affinity uptake.