The importance of eukaryotic ferritins in iron handling and cytoprotection

Arosio, Paolo; Carmona, Fernando; Gozzelino, Raffaella; Maccarinelli, Federica; Poli, Maura

doi:10.1042/bj20150787

Cited by 87 publications

(75 citation statements)

References 175 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Iron taken up by enterocytes can be used directly for intrinsic cellular metabolic processes, stored, or exported across the basolateral membrane for systemic delivery. Iron is stored in enterocytes, like other cells, largely in the form of ferritin, which is comprised of a spherical nanocage of heavy (H) and light (L) chains surrounding a core of iron that is oxidized by H‐ferritin . This allows iron to be stored in an inert form that limits the production of damaging redox reactive species.…”

Section: Iron Absorption and Recyclingmentioning

confidence: 99%

Overview of iron metabolism in health and disease

Dev

Babitt

2017

Hemodialysis International

360

269

View full text Add to dashboard Cite

Iron is an essential element for numerous fundamental biologic processes, but excess iron is toxic. Abnormalities in systemic iron balance are common in patients with chronic kidney disease (CKD) and iron administration is a mainstay of anemia management in many patients. This review provides an overview of the essential role of iron in biology, the regulation of systemic and cellular iron homeostasis, how imbalances in iron homeostasis contribute to disease, and the implications for CKD patients.

show abstract

Section: Iron Absorption and Recyclingmentioning

confidence: 99%

Overview of iron metabolism in health and disease

Dev

Babitt

2017

Hemodialysis International

360

269

View full text Add to dashboard Cite

show abstract

“…Ft is highly stable at a wide range of temperatures and acidities, and sequesters Fe 2+ ions in ferroxidase centres of the Ft subunits. These ferroxidase centres have the important ability to consume all reagents of the radical Fenton reactions (see the Brain iron overload and toxicity section) and thereby inhibit iron-mediated oxidative stress 15. Ft is expressed in microglia and macrophages, but it is also found in some neurons 16.…”

Section: Iron Homeostasis In Normal Brainmentioning

confidence: 99%

Brain iron overload following intracranial haemorrhage

et al. 2016

View full text Add to dashboard Cite

Intracranial haemorrhages, including intracerebral haemorrhage (ICH), intraventricular haemorrhage (IVH) and subarachnoid haemorrhage (SAH), are leading causes of morbidity and mortality worldwide. In addition, haemorrhage contributes to tissue damage in traumatic brain injury (TBI). To date, efforts to treat the long-term consequences of cerebral haemorrhage have been unsatisfactory. Incident rates and mortality have not showed significant improvement in recent years. In terms of secondary damage following haemorrhage, it is becoming increasingly apparent that blood components are of integral importance, with haemoglobin-derived iron playing a major role. However, the damage caused by iron is complex and varied, and therefore, increased investigation into the mechanisms by which iron causes brain injury is required. As ICH, IVH, SAH and TBI are related, this review will discuss the role of iron in each, so that similarities in injury pathologies can be more easily identified. It summarises important components of normal brain iron homeostasis and analyses the existing evidence on iron-related brain injury mechanisms. It further discusses treatment options of particular promise.

show abstract

“…1B) symmetry axes and six channels in correspondence with the three 4-fold (C4, see Fig. 1C) symmetry axes of the octahedral point symmetry of the cage (1,2). Despite many similarities across ferritins expressed in different species, the interiors of the C3 and C4 channels are quite variable, showing substantial differences in terms of hydrophobicity/hydrophilicity and electric charge distributions when comparing vertebrate ferritins with those from plants, bacteria, or archaea (3,4).…”

mentioning

confidence: 99%

Electrostatic and Structural Bases of Fe2+ Translocation through Ferritin Channels

Chandramouli

Bernacchioni

Maio

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by F. Peter GuengerichFerritin molecular cages are marvelous 24-mer supramolecular architectures that enable massive iron storage (>2000 iron atoms) within their inner cavity. This cavity is connected to the outer environment by two channels at C3 and C4 symmetry axes of the assembly. Ferritins can also be exploited as carriers for in vivo imaging and therapeutic applications, owing to their capability to effectively protect synthetic non-endogenous agents within the cage cavity and deliver them to targeted tissue cells without stimulating adverse immune responses. Recently, X-ray crystal structures of Fe 2؉ -loaded ferritins provided important information on the pathways followed by iron ions toward the ferritin cavity and the catalytic centers within the protein. However, the specific mechanisms enabling Fe 2؉ uptake through wild-type and mutant ferritin channels is largely unknown. To shed light on this question, we report extensive molecular dynamics simulations, site-directed mutagenesis, and kinetic measurements that characterize the transport properties and translocation mechanism of Fe 2؉ through the two ferritin channels, using the wild-type bullfrog Rana catesbeiana H protein and some of its variants as case studies. We describe the structural features that determine Fe 2؉ translocation with atomistic detail, and we propose a putative mechanism for Fe 2؉ transport through the channel at the C3 symmetry axis, which is the only iron-permeable channel in vertebrate ferritins. Our findings have important implications for understanding how ion permeation occurs, and further how it may be controlled via purposely engineered channels for novel biomedical applications based on ferritin.Twenty-four-mer ferritins are ubiquitous iron storage proteins that share a common architecture: a protein nanocage (see Fig. 1A) assembled from subunits made up by a 4-helix bundle (helices H1-H4) structure completed by a short C-terminal helix, H5, and a long loop connecting helices H2 and H3. This protein shell surrounds an 8-nm inner cage connected to the external environment by two different types of channels: eight channels in correspondence with the four 3-fold (C3, see Fig. 1B) symmetry axes and six channels in correspondence with the three 4-fold (C4, see Fig. 1C) symmetry axes of the octahedral point symmetry of the cage (1, 2). Despite many similarities across ferritins expressed in different species, the interiors of the C3 and C4 channels are quite variable, showing substantial differences in terms of hydrophobicity/hydrophilicity and electric charge distributions when comparing vertebrate ferritins with those from plants, bacteria, or archaea (3, 4). In turn, the specific chemical nature of these channels directly affects their transport properties and determines the preferred pathways followed by ferrous ions from the exterior of the cage to the catalytic ferroxidase center within the internal cavity. In vertebrate ferritins, for example, the C4 channels (about 12 Å in length) are relatively narrow and mai...

show abstract

The importance of eukaryotic ferritins in iron handling and cytoprotection

Cited by 87 publications

References 175 publications

Overview of iron metabolism in health and disease

Overview of iron metabolism in health and disease

Brain iron overload following intracranial haemorrhage

Electrostatic and Structural Bases of Fe2+ Translocation through Ferritin Channels

Contact Info

Product

Resources

About