Ferritin Protein Regulates the Degradation of Iron Oxide Nanoparticles

Proteins implicated in iron homeostasis are assumed to be also involved in the cellular processing of iron oxide nanoparticles. In this work, the role of an endogenous iron storage protein—namely the ferritin—is examined in the remediation and biodegradation of magnetic iron oxide nanoparticles. Previous in vivo studies suggest the intracellular transfer of the iron ions released during the degradation of nanoparticles to endogenous protein cages within lysosomal compartments. Here, the capacity of ferritin cages to accommodate and store the degradation products of nanoparticles is investigated in vitro in the physiological acidic environment of the lysosomes. Moreover, it is questioned whether ferritin proteins can play an active role in the degradation of the nanoparticles. The magnetic, colloidal, and structural follow‐up of iron oxide nanoparticles and proteins in lysosome‐like medium confirms the efficient remediation of potentially harmful iron ions generated by nanoparticles within ferritins. The presence of ferritins, however, delays the degradation of particles due to a complex colloidal behavior of the mixture in acidic medium. This study exemplifies the important implications of intracellular proteins in processes of degradation and metabolization of iron oxide nanoparticles.     

Co-products of beef processing enhance non-haem iron absorption in an in vitro digestion/caco-2 cell model

Beef processing produces high volumes of protein rich, low value, ‘waste’ co-products such as offal. Beef improves uptake of low bioavailable non-haem iron (found in vegetables, fortificants, supplements) and this effect is dubbed the ‘meat-factor’, although the underlying mechanism is not fully understood. Here, we investigate whether bovine co-products (kidney, lung, heart) not previously studied share this enhancing potential. This was determined by coupled in vitro digestion of co-products and subsequent caco-2 cell ferritin formation (an intracellular iron storage protein). In this study we show that bovine co-products significantly increase caco-2 cells’ response to non-haem iron from infant rice cereal. The presence of these co-products, (kidney, lung and heart), increased relative uptake (by 207.13%, 171.21%, 265.28%, respectively), to a greater extent than beef (30.23%). Our findings present a novel function for co-products of beef processing that may have potential as food ingredients to improve non-haem iron bioavailability, thus adding value.     

High Iron and Iron Household Protein Contents in Perineuronal Net-Ensheathed Neurons Ensure Energy Metabolism with Safe Iron Handling

A subpopulation of neurons is less vulnerable against iron-induced oxidative stress and neurodegeneration. A key feature of these neurons is a special extracellular matrix composition that forms a perineuronal net (PN). The PN has a high affinity to iron, which suggests an adapted iron sequestration and metabolism of the ensheathed neurons. Highly active, fast-firing neurons—which are often ensheathed by a PN—have a particular high metabolic demand, and therefore may have a higher need in iron. We hypothesize that PN-ensheathed neurons have a higher intracellular iron concentration and increased levels of iron proteins. Thus, analyses of cellular and regional iron and the iron proteins transferrin (Tf), Tf receptor 1 (TfR), ferritin H/L (FtH/FtL), metal transport protein 1 (MTP1 aka ferroportin), and divalent metal transporter 1 (DMT1) were performed on Wistar rats in the parietal cortex (PC), subiculum (SUB), red nucleus (RN), and substantia nigra (SNpr/SNpc). Neurons with a PN (PN⁺) have higher iron concentrations than neurons without a PN: PC 0.69 mM vs. 0.51 mM, SUB 0.84 mM vs. 0.69 mM, SN 0.71 mM vs. 0.63 mM (SNpr)/0.45 mM (SNpc). Intracellular Tf, TfR and MTP1 contents of PN⁺ neurons were consistently increased. The iron concentration of the PN itself is not increased. We also determined the percentage of PN⁺ neurons: PC 4%, SUB 5%, SNpr 45%, RN 86%. We conclude that PN⁺ neurons constitute a subpopulation of resilient pacemaker neurons characterized by a bustling iron metabolism and outstanding iron handling capabilities. These properties could contribute to the low vulnerability of PN⁺ neurons against iron-induced oxidative stress and degeneration.     

Short communication: Bovine α-casein is a ferritin-binding protein and inhibitory factor of milk ferritin immunoassay

Commercial bovine milk α-casein, but not β- and κ-caseins, bound to bovine spleen ferritin, as determined by an immunoassay for ferritin. In contrast, α-casein did not bind to apoferritin. The binding of α-casein to bovine spleen ferritin was strongly inhibited by increasing ionic strength by the addition of 0.5 M (NH₄)₂SO₄. The addition of α-casein to a known amount of bovine spleen ferritin resulted in significantly lower recovery (78-80%) of added ferritin, although β- and κ-caseins showed little inhibitory effect in the ferritin immunoassay. These results indicate that bovine α-casein is a specific ferritin-binding protein that may inhibit milk ferritin immunoassay.     

Ferritinophagy and α-Synuclein: Pharmacological Targeting of Autophagy to Restore Iron Regulation in Parkinson’s Disease

A major hallmark of Parkinson’s disease (PD) is the fatal destruction of dopaminergic neurons within the substantia nigra pars compacta. This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of α-synuclein protein aggregates. A triad contribution of α-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Elevated intracellular iron concentrations up-regulate ferritin expression, an iron storage protein that provides cytoprotection against redox stress. The lysosomal degradation pathway, autophagy, can release iron from ferritin stores to facilitate its trafficking in a process termed ferritinophagy. Aggregated α-synuclein inhibits SNARE protein complexes and destabilizes microtubules to halt vesicular trafficking systems, including that of autophagy effectively. The scope of this review is to describe the physiological and pathological relationship between iron regulation and α-synuclein, providing a detailed understanding of iron metabolism within nigral neurons. The underlying mechanisms of autophagy and ferritinophagy are explored in the context of PD, identifying potential therapeutic targets for future investigation.     

Kiyoteru Tokuyasu: a pioneer of cryo‐ultramicrotomy

In July 2015 Professor K.T. Tokuyasu passed away in San Diego giving us the opportunity to reflect on the contribution this electron microscopist made to the field of immunocytochemistry. His work provided a sensitive, minimally invasive approach to producing thin sections of biological material for labeling with antibodies. His approach has been applied to a wide range of biological applications and provided important information on cellular processes.