A Comparison of Conserved Features in the Human Coronavirus Family Shows That Studies of Viruses Less Pathogenic than SARS-CoV-2, Such as HCoV-OC43, Are Good Model Systems for Elucidating Basic Mechanisms of Infection and Replication in Standard Laboratories.

In 2021, at the height of the COVID-19 pandemic, coronavirus research spiked, with over 83,000 original research articles related to the word "coronavirus" added to the online resource . Just 2 years later, in 2023, only 30,900 original research articles related to the word "coronavirus" were added. While, irrefutably, the funding of coronavirus research drastically decreased, a possible explanation for the decrease in interest in coronavirus research is that projects on SARS-CoV-2, the causative agent of COVID-19, halted due to the challenge of establishing a good cellular or animal model system.

In-Gel Activity Assay of Mammalian Mitochondrial and Cytosolic Aconitases, Surrogate Markers of Compartment-Specific Oxidative Stress and Iron Status.

Two aconitase isoforms are present in mammalian cells: the mitochondrial aconitase (ACO2) that catalyzes the reversible isomerization of citrate to isocitrate in the citric acid cycle, and the bifunctional cytosolic enzyme (ACO1), which also plays a role as an RNA-binding protein in the regulation of intracellular iron metabolism. Aconitase activities in the different subcellular compartments can be selectively inactivated by different genetic defects, iron depletion, and oxidative or nitrative stress. Aconitase contains a [4Fe-4S] cluster that is essential for substrate coordination and catalysis.

A bulge uridine in the HIF2α IRE allows IRP1 but not IRP2 to selectively regulate HIF2α expression and ensuing EPO levels.

Iron regulatory proteins (IRP1 and IRP2) play a pivotal role in maintaining cellular iron homeostasis by binding to iron-responsive elements (IREs) of target messenger RNAs and regulating the expression of these iron-related genes. Mice and humans who lack functional IRP1 develop erythrocytosis due to erythropoietin (EPO) overproduction, whereas those who lack IRP2 develop microcytic anemia, believed to result from iron deficiency of erythroblasts. Here, we discovered that IRP2 deficiency reduced the expression of hypoxia-inducible factor 2α (HIF2α) and its transcriptional target, EPO, thereby compromising the stress erythropoiesis response to generate red blood cells upon anemia.

Ablation of Iron Regulatory Protein 2 produces a neurological disorder characterized by motor, somatosensory, and executive dysfunction in mice.

Iron is an important cofactor for many proteins and is used to create Fe-S clusters and heme prosthetic groups that enzymes use to catalyze enzymatic reactions. Proteins involved in the import, export, and sequestration of iron are regulated by Iron Regulatory Proteins (IRPs). Recently, a patient with bi-allelic loss of function mutations in IREB2 leading to the absence of IRP2 protein was discovered.