GNPS - A novel iron chaperone complex delivers iron to the cytosolic [2Fe-2S] cluster distribution system
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ Orbitrap XL
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
James Wohlschlegel
PROVIDER: MSV000083887 | GNPS | Tue Jun 04 08:24:00 BST 2019
REPOSITORIES: GNPS
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Project description:DC3000 cultures were grown under highly controlled conditions and after the addition of iron citrate or sodium citrate to the media. In the cultures supplemented with iron, we found that cell-associated iron increased rapidly while culture densities were not significantly different over 4 hours when compared to cultures with sodium citrate added. Microarray analysis of samples taken from before and after the addition of either sodium citrate or iron citrate identified 386 differentially regulated genes with high statistical confidence. Differentially regulated genes were clustered based on expression patterns observed between comparison of samples taken at different time points and with different supplements. This analysis grouped genes associated with the same regulatory motifs and/or had similar putative or known function. Keywords: iron response, environmental signal, time course 5 biological replicates, 3 timepoint: 0h, 0.5h, 4h after addition of iron citrate or sodium citrate to increase final concentration by 50uM
2008-11-07 | E-GEOD-13500 | biostudies-arrayexpress
Project description:Plastids surrounded by four membranes harbor a special compartment between the outer and inner plastid membrane pair, the so-called periplastidal compartment (PPC). This cellular structure is usually presumed to be the reduced cytoplasm of a eukaryotic phototrophic endosymbiont, which was integrated into a host cell and streamlined into a plastid with a complex membrane structure. Up to date, no mitochondrion or mitochondrion-related organelle has been identified in the PPC of any representative. However, two prominent groups, the cryptophytes and the chlorarachniophytes, still harbor a reduced cell nucleus of symbiont origin, the nucleomorph, in their PPCs. Generally, many cytoplasmic and nucleus-located eukaryotic proteins need an iron-sulfur cofactor for their functionality. Beside some exceptions, their synthesis is depending on a so-called iron-sulfur complex (ISC) assembly machinery located in the mitochondrion. This machinery provides the cytoplasm with a still unknown sulfur component, which is then converted into iron-sulfur clusters via a cytosolic iron-sulfur protein assembly (CIA) machinery. Here, we investigated if a CIA machinery is present in mitochondrion-lacking PPCs. By using bioinformatic screens and in vivo-localizations of candidate proteins, we show that the presence of a PPC-specific CIA machinery correlates with the presence of a nucleomorph. Phylogenetic analyses of PPC- and host specific CIA components additionally indicate a complex evolution of the CIA machineries in organisms having plastids surrounded by four membranes.
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Project description:Cells contain hundreds of proteins that require iron cofactors for activity. Iron cofactors are synthesized in the cell, but the pathways involved in distributing heme, iron-sulfur clusters, and ferrous/ferric ions to apoproteins remain incompletely defined. In particular, cytosolic monothiol glutaredoxins and BolA-like proteins have been identified as [2Fe-2S]-coordinating complexes in vitro and iron-regulatory proteins in fungi, but it is not clear how these proteins function in mammalian systems or how this complex might affect Fe-S proteins or the cytosolic Fe-S assembly machinery. To explore these questions, we use quantitative immunoprecipitation and live cell proximity-dependent biotinylation to monitor interactions between Glrx3, BolA2, and components of the cytosolic iron-sulfur cluster assembly system. We characterize cytosolic Glrx3·BolA2 as a [2Fe-2S] chaperone complex in human cells. Unlike complexes formed by fungal orthologs, human Glrx3-BolA2 interaction required the coordination of Fe-S clusters, whereas Glrx3 homodimer formation did not. Cellular Glrx3·BolA2 complexes increased 6-8-fold in response to increasing iron, forming a rapidly expandable pool of Fe-S clusters. Fe-S coordination by Glrx3·BolA2 did not depend on Ciapin1 or Ciao1, proteins that bind Glrx3 and are involved in cytosolic Fe-S cluster assembly and distribution. Instead, Glrx3 and BolA2 bound and facilitated Fe-S incorporation into Ciapin1, a [2Fe-2S] protein functioning early in the cytosolic Fe-S assembly pathway. Thus, Glrx3·BolA is a [2Fe-2S] chaperone complex capable of transferring [2Fe-2S] clusters to apoproteins in human cells.
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