TY  - JOUR
A1  - Schwarz, Maria
A1  - Lossow, Kristina
A1  - Kopp, Johannes Florian
A1  - Schwerdtle, Tanja
A1  - Kipp, Anna Patricia
T1  - Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper
JF  - Nutrients
N2  - Trace elements, like Cu, Zn, Fe, or Se, are important for the proper functioning of antioxidant enzymes. However, in excessive amounts, they can also act as pro-oxidants. Accordingly, trace elements influence redox-modulated signaling pathways, such as the Nrf2 pathway. Vice versa, Nrf2 target genes belong to the group of transport and metal binding proteins. In order to investigate whether Nrf2 directly regulates the systemic trace element status, we used mice to study the effect of a constitutive, whole-body Nrf2 knockout on the systemic status of Cu, Zn, Fe, and Se. As the loss of selenoproteins under Se-deprived conditions has been described to further enhance Nrf2 activity, we additionally analyzed the combination of Nrf2 knockout with feeding diets that provide either suboptimal, adequate, or supplemented amounts of Se. Experiments revealed that the Nrf2 knockout partially affected the trace element concentrations of Cu, Zn, Fe, or Se in the intestine, liver, and/or plasma. However, aside from Fe, the other three trace elements were only marginally modulated in an Nrf2-dependent manner. Selenium deficiency mainly resulted in increased plasma Zn levels. One putative mediator could be the metal regulatory transcription factor 1, which was up-regulated with an increasing Se supply and downregulated in Se-supplemented Nrf2 knockout mice.
KW  - Nrf2
KW  - selenium
KW  - iron
KW  - copper
KW  - zinc
KW  - homeostasis
Y1  - 2019
U6  - https://doi.org/10.3390/nu11092112
SN  - 2072-6643
VL  - 11
IS  - 9
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Mendel, Ralf R.
A1  - Hercher, Thomas W.
A1  - Zupok, Arkadiusz
A1  - Hasnat, Muhammad Abrar
A1  - Leimkühler, Silke
T1  - The requirement of inorganic Fe-S clusters for the biosynthesis of the organometallic molybdenum cofactor
JF  - Inorganics : open access journal
N2  - Iron-sulfur (Fe-S) clusters are essential protein cofactors. In enzymes, they are present either in the rhombic [2Fe-2S] or the cubic [4Fe-4S] form, where they are involved in catalysis and electron transfer and in the biosynthesis of metal-containing prosthetic groups like the molybdenum cofactor (Moco). Here, we give an overview of the assembly of Fe-S clusters in bacteria and humans and present their connection to the Moco biosynthesis pathway. In all organisms, Fe-S cluster assembly starts with the abstraction of sulfur froml-cysteine and its transfer to a scaffold protein. After formation, Fe-S clusters are transferred to carrier proteins that insert them into recipient apo-proteins. In eukaryotes like humans and plants, Fe-S cluster assembly takes place both in mitochondria and in the cytosol. Both Moco biosynthesis and Fe-S cluster assembly are highly conserved among all kingdoms of life. Moco is a tricyclic pterin compound with molybdenum coordinated through its unique dithiolene group. Moco biosynthesis begins in the mitochondria in a Fe-S cluster dependent step involving radical/S-adenosylmethionine (SAM) chemistry. An intermediate is transferred to the cytosol where the dithiolene group is formed, to which molybdenum is finally added. Further connections between Fe-S cluster assembly and Moco biosynthesis are discussed in detail.
KW  - Moco biosynthesis
KW  - Fe-S cluster assembly
KW  - l-cysteine desulfurase
KW  - ISC
KW  - SUF
KW  - NIF
KW  - iron
KW  - molybdenum
KW  - sulfur
Y1  - 2020
U6  - https://doi.org/10.3390/inorganics8070043
SN  - 2304-6740
VL  - 8
IS  - 7
PB  - MDPI
CY  - Basel
ER  -