The Iron Metallome in Eukaryotic Organisms

Dlouhy, Adrienne C.; Outten, Caryn E.

doi:10.1007/978-94-007-5561-1_8

Cited by 110 publications

(95 citation statements)

References 114 publications

(167 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The molecular understanding of factors involved in iron-responsive transcriptional regulation in eukaryotes is still in its infancy (4,7,8). Both their underlying mechanisms and their sensed molecules are usually not well known.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, organisms have developed sophisticated and largely divergent strategies to acquire appropriate cellular iron levels and to avoid iron overloading (5)(6)(7). Except for vertebrates, which regulate cellular iron homeostasis mainly on the level of translation by the iron-regulatory proteins IRP1 and IRP2, transcriptional control of iron-responsive gene expression is widespread (7).…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Basic Leucine Zipper Stress Response Regulator Yap5 Senses High-Iron Conditions by Coordination of [2Fe-2S] Clusters

Rietzschel

Pierik

Bill

et al. 2015

Molecular and Cellular Biology

View full text Add to dashboard Cite

Iron is an essential, yet at elevated concentrations toxic trace element. To date, the mechanisms of iron sensing by eukaryotic iron-responsive transcription factors are poorly understood. The Saccharomyces cerevisiae transcription factor Yap5, a member of the Yap family of bZIP stress response regulators, administrates the adaptive response to high-iron conditions. Despite the central role of the iron-sensing process for cell viability, the molecule perceived by Yap5 and the underlying regulatory mechanisms are unknown. Here, we show that Yap5 senses high-iron conditions by two Fe/S clusters bound to its activator domain (Yap5-AD). The more stable iron-regulatory Fe/S cluster at the N-terminal cysteine-rich domain (n-CRD) of Yap5 is detected in vivo and in vitro. Iron is a key trace element for virtually all organisms. It functions as an essential cofactor in electron transfer, metabolite biosynthesis, DNA metabolism, and protein translation. Although iron is highly abundant, its bioavailability is low due to its poor solubility under ambient conditions (1, 2). For microbial pathogens, iron acquisition from their host cells is frequently crucial for their virulence. Hence, mutations in microbial genes involved in iron acquisition or utilization are associated with the loss of pathogenicity (3, 4). On the other hand, high intracellular iron levels are both a source and an amplifier of reactive oxygen species and thus highly toxic.Iron acquisition, transport and storage need to be tightly regulated, and disruption or deregulation of iron-related molecules can have significant health consequences. Hence, organisms have developed sophisticated and largely divergent strategies to acquire appropriate cellular iron levels and to avoid iron overloading (5-7). Except for vertebrates, which regulate cellular iron homeostasis mainly on the level of translation by the iron-regulatory proteins IRP1 and IRP2, transcriptional control of iron-responsive gene expression is widespread (7). In a large number of fungi, iron-responsive gene expression is conferred by the interplay of two conserved transcriptional repressors. Of these, the GATAtype transcription factor SreA regulates the expression of genes involved in iron uptake, while the basic leucine zipper (bZIP) transcription factor HapX regulates the iron-responsive expression of genes involved in iron-consuming pathways through interaction with the CCAAT-binding complex CBC (4,8).The model organism Saccharomyces cerevisiae utilizes three iron-responsive transcription factors. Aft1 and Aft2 play a central role in iron-dependent transcription activation of genes encoding components involved in cellular uptake and intracellular distribution of iron (9, 10). Yap5 is involved in the detoxification of excess iron by inducing the transcription of, e.g., CCC1 encoding the only known iron importer into the vacuole, the major metal storage organelle in fungi (11,12). Yap5 belongs to a fungus-specific family of stress response regulators that contains eight members in S. cerevisiae (...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Basic Leucine Zipper Stress Response Regulator Yap5 Senses High-Iron Conditions by Coordination of [2Fe-2S] Clusters

Rietzschel

Pierik

Bill

et al. 2015

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…Many different structural and enzymatic proteins contain iron, which is essential to their function [170]. Iron is taken by food where it is found in a divalent (Fe 21 ) or trivalent 687 Biochemical Parameters in Toxicological Studies in Africa (Fe 31 ) form.…”

Section: Ironmentioning

confidence: 99%

Biochemical Parameters in Toxicological Studies in Africa

Dzoyem

Kuete

Eloff

2014

Toxicological Survey of African Medicinal Plants

View full text Add to dashboard Cite

“…It also serves as the donor and acceptor of electrons in many metabolic processes (Ponka, 1997;Lill, 2009). Moreover, iron can be utilized as a cofactor in the formation of functional iron-sulfur (Fe-S) cluster proteins, hemebinding proteins, and diiron proteins (Dlouhy and Outten, 2013;Heath et al, 2013;Zhang, 2014), which extensively function in electron transfer, ribosome maturation, genome stability, as well as cell cycle control (Rouault and Klausner, 1997;Kaplan et al, 2006;Ye and Rouault, 2010;White and Dillingham, 2012;Zhang, 2014). In eukaryotes, iron overload and iron deficiency are the two main iron disorders.…”

Section: Introductionmentioning

confidence: 99%

The correlation between iron homeostasis and telomere maintenance

Zhang

2014

Front. Biol.

View full text Add to dashboard Cite

Eukaryotic organisms require iron to sustain genome stability, cell proliferation and development. Chromosomes contain telomeres to ensure complete replications and avoid fusions. Numerous evidences reveal that iron can act directly or indirectly on telomere maintenance. In human, disruption of systemic or cellular iron homeostasis is reportedly to cause serious health problems such as iron overload (hereditary hemochromatosis), iron deficiency anemia, carcinogenesis and acceleration of aging process. These processes commonly associate with abnormal telomere length. Additionally, cells containing mutations in iron-containing proteins such as DNA polymerases (Polα, δ, and ε), regulator of telomere length 1 (RTEL1) and the small subunit of ribonucleotide reductases (RNRs) have abnormal telomere length. This review briefly summarizes current understandings on iron homeostasis and telomere maintenance in cancer and aging process, followed by discussing their direct and indirect correlation, and the possible regulatory mechanisms.

show abstract

The Iron Metallome in Eukaryotic Organisms

Cited by 110 publications

References 114 publications

The Basic Leucine Zipper Stress Response Regulator Yap5 Senses High-Iron Conditions by Coordination of [2Fe-2S] Clusters

The Basic Leucine Zipper Stress Response Regulator Yap5 Senses High-Iron Conditions by Coordination of [2Fe-2S] Clusters

Biochemical Parameters in Toxicological Studies in Africa

The correlation between iron homeostasis and telomere maintenance

Contact Info

Product

Resources

About