The ins and outs of iron: Escorting iron through the mammalian cytosol

Philpott, Caroline C.; Jadhav, Shyamalagauri

doi:10.1016/j.freeradbiomed.2018.10.411

Cited by 77 publications

(62 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both PCBPs are iron chaperones that can bind and deliver iron, in addition to their functions as RBPs . Interestingly, we observed no relationship between the poly(C)‐ and iron‐binding abilities of either PCBP1 or PCBP2 (Fig ).…”

Section: Resultsmentioning

confidence: 68%

“…Although previous studies have demonstrated that phosphorylation of PCBP1 results in the loss of polyribonucleotide binding ability [21,22], we did not observe any phosphorylated PCBP1 or PCBP2 after TLR9 stimulation in macrophages (data not shown), suggesting that phosphorylation of PCBP1 and/or PCBP2 did not trigger destabilization of sortilin mRNA in response to TLR signals. Both PCBPs are iron chaperones that can bind and deliver iron, in addition to their functions as RBPs [23]. Interestingly, we observed no relationship between the poly(C)-and iron-binding abilities of either PCBP1 [17] or PCBP2 (Fig 4).…”

Section: Zn 2+ Affects the Nucleotide Binding Activity Of Pcbp2mentioning

confidence: 73%

See 1 more Smart Citation

PCBP2 post‐transcriptionally regulates sortilin expression by binding to a C‐rich element in its 3′ UTR

2020

Self Cite

View full text Add to dashboard Cite

Post‐transcriptional regulation of cytokine production is crucial to ensure appropriate immune responses. We previously demonstrated that poly‐rC‐binding protein‐1 (PCBP1) can act as a trans‐acting factor to stabilize transcripts encoding sortilin, which mediates cytokine trafficking. Here, we report that PCBP2, which strongly resembles PCBP1, can stabilize sortilin transcripts in macrophages using the same mechanism employed by PCBP1. PCBP2 recognized the C‐rich element in the 3′ UTR of sortilin mRNA, and PCBP2 knockdown decreased sortilin transcripts, indicating that PCBP2 stabilizes sortilin mRNA by binding to its 3′ UTR. Zn2+ reversibly inhibited the nucleotide binding ability of PCBP2 in vitro. These findings suggest that both PCBP2 and PCBP1 may control the stability of sortilin transcripts by sensing intracellular Zn2+ levels in immune cells.

show abstract

Section: Resultsmentioning

confidence: 68%

Section: Zn 2+ Affects the Nucleotide Binding Activity Of Pcbp2mentioning

confidence: 73%

PCBP2 post‐transcriptionally regulates sortilin expression by binding to a C‐rich element in its 3′ UTR

2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Dietary iron exists largely in two valency forms: the reduced, reactive, and toxic ferrous ion (Fe 2þ ) form present in heme-iron and the oxidized and relatively non-toxic ferric ion (Fe 3þ ) form in non-heme iron. [3][4][5] Both heme and non-heme are taken up by enterocytes lining the intestinal brush border. 3,4 Non-heme iron is transported through the apical membrane of enterocytes through DMT1 (divalent metal transporter-1), a transmembrane transporter (Figure 1).…”

Section: Iron Transportmentioning

confidence: 99%

“…[3][4][5] Both heme and non-heme are taken up by enterocytes lining the intestinal brush border. 3,4 Non-heme iron is transported through the apical membrane of enterocytes through DMT1 (divalent metal transporter-1), a transmembrane transporter (Figure 1). 3,[5][6][7] Transport through DMT1 requires reduction of Fe 3þ to Fe 2þ which is performed by duodenal cytochrome B (Dycb), a ferrireductase also localized at the apical membrane of the enterocytes.…”

Section: Iron Transportmentioning

confidence: 99%

See 1 more Smart Citation

Overdosing on iron: Elevated iron and degenerative brain disorders

D’Mello¹,

Kindy

2020

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

All cells in organisms ranging from yeast to humans utilize iron as a cofactor or structural element of proteins that function in diverse and critical cellular functions. However, deregulation of the homeostatic mechanisms regulating iron metabolism resulting in a reduction or excess of iron within the cell or outside of it can have serious effects to the health of cells and the organism. This review provides a brief overview of the molecular and cellular mechanisms regulating iron physiology, including the molecules and processes regulating iron uptake, its storage and utilization, its recycling, and its release from the cell, such that the cellular iron levels are sufficient to meet metabolic demand but below those that cause permanent damage. The major focus of review is on the pathological consequences of dysregulation of these homeostatic mechanisms, focusing on the brain. Current advances on the role of iron accumulation to the pathogenesis of rare neurological disorders caused by genetic mutations as well as to the more prevalent and age-associated neurodegenerative diseases are described. Impact statement Brain degenerative disorders, which include some neurodevelopmental disorders and age-associated diseases, cause debilitating neurological deficits and are generally fatal. A large body of emerging evidence indicates that iron accumulation in neurons within specific regions of the brain plays an important role in the pathogenesis of many of these disorders. Iron homeostasis is a highly complex and incompletely understood process involving a large number of regulatory molecules. Our review provides a description of what is known about how iron is obtained by the body and brain and how defects in the homeostatic processes could contribute to the development of brain diseases, focusing on Alzheimer’s disease and Parkinson’s disease as well as four other disorders belonging to a class of inherited conditions referred to as neurodegeneration based on iron accumulation (NBIA) disorders. A description of potential therapeutic approaches being tested for each of these different disorders is provided.

show abstract

Hsp90 and metal‐binding J‐protein family chaperones are not critically involved in cellular iron–sulfur protein assembly and iron regulation in yeast

et al. 2023

View full text Add to dashboard Cite

Systematic studies have revealed interactions between components of the Hsp90 chaperone system and Fe/S protein biogenesis or iron regulation. In addition, two chloroplast-localized DnaJ-like proteins, DJA5 and DJA6, function as specific iron donors in plastidial Fe/S protein biogenesis. Here, we used Saccharomyces cerevisiae to study the impact of both the Hsp90 chaperone and the yeast DJA5-DJA6 homologs, the essential cytosolic Ydj1, and the mitochondrial Mdj1, on cellular iron-related processes. Despite severe phenotypes induced upon depletion of these crucial proteins, there was no critical in vivo impact on Fe/S protein biogenesis or iron regulation. Importantly, unlike the plant DJA5-DJA6 iron chaperones, Ydj1 and Mdj1 did not bind iron in vivo, suggesting that these proteins use zinc for function under normal physiological conditions.

show abstract

The ins and outs of iron: Escorting iron through the mammalian cytosol

Cited by 77 publications

References 59 publications

PCBP2 post‐transcriptionally regulates sortilin expression by binding to a C‐rich element in its 3′ UTR

PCBP2 post‐transcriptionally regulates sortilin expression by binding to a C‐rich element in its 3′ UTR

Overdosing on iron: Elevated iron and degenerative brain disorders

Hsp90 and metal‐binding J‐protein family chaperones are not critically involved in cellular iron–sulfur protein assembly and iron regulation in yeast

Contact Info

Product

Resources

About