SARS-CoV-2-induced hypomethylation of the ferritin heavy chain (FTH1) gene underlies serum hyperferritinemia in severe COVID-19 patients

Muhammad, Jibran Sualeh; ElGhazali, Gehad; Shafarin, Jasmin; Mohammad, Mohammad G.; Abu-Qiyas, Ameera; Hamad, Mawieh

doi:10.1016/j.bbrc.2022.09.083

Cited by 7 publications

(2 citation statements)

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“…Moreover, expression levels of HBA1 (Figures 2B and 2E) and HBA2 (Figure 2B), which produce alpha globin carrying oxygen to cells and tissues throughout the body, are high in severe COVID-19. Another two genes, GRINA and FTL (Figure 2E), were also differentially expressed between severe COVID-19 patients and controls [27], [28].…”

Section: Sr2 Links the Activities Of Genes To Biological Conditionsmentioning

confidence: 93%

SR2: Sparse Representation Learning for Scalable Single-cell RNA Sequencing Data Analysis

Zhao

Lin

2023

Preprint

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Single-cell RNA-sequencing (scRNA-seq) technology has been widely used to measure the transcriptome of cells in complex and heterogeneous systems. Integrative analysis of multiple scRNA-seq data can transform our understanding of various aspects of biology at the single-cell level. Many computational methods are proposed for data integration. However, few methods for scRNA-seq data integration explicitly model variation from heterogeneous biological conditions for interpretation. Modeling the variation helps understand the effect of biological conditions on complex biological systems.Our study proposes SR2 to capture gene expression patterns from heterogeneous biological conditions and discover cell identity simultaneously. Therefore, it can uncover the effect of biological conditions on the gene expression of cells and simultaneously achieve state-of-the-performance in cell identity discovery in our comprehensive comparison. Notably, SR2 is extended to model the effects of biological conditions on gene expression for cell populations, thus uncovering the effect of biological conditions on gene expression for cell populations and identifying putative condition-associated cell populations. To improve its scalability, we incorporate a batch-fitting strategy to ensure it is scalable to scRNA-seq data with arbitrary sample sizes. Moreover, the broad applicability of SR2 in biomedical studies has been demonstrated via applications. The complete package of SR2 is available athttps://github.com/kai0511/SR2.

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Section: Sr2 Links the Activities Of Genes To Biological Conditionsmentioning

confidence: 93%

SR2: Sparse Representation Learning for Scalable Single-cell RNA Sequencing Data Analysis

Zhao

Lin

2023

Preprint

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“…In mitochondria, organelle-specific ferritin rescues mitochondrial iron overload and dysfunction [ 118 ]. During COVID-19 infection, hypomethylation of the ferritin heavy-chain gene underlies serum hyperferritinemia and low levels of serum iron in severely ill COVID-19 patients [ 119 ]. Prolonged Hif1α activity and higher miRNA210 expression downregulate the iron–sulfur cluster assembly machinery (ISCU) and divalent metal transporter 1 (DMT1) expression ( Figure 3 ).…”

Section: Cellular Mechanisms To Cope With the Energy Crisismentioning

confidence: 99%

Why Is Iron Deficiency/Anemia Linked to Alzheimer’s Disease and Its Comorbidities, and How Is It Prevented?

Fehsel

2023

Biomedicines

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Impaired iron metabolism has been increasingly observed in many diseases, but a deeper, mechanistic understanding of the cellular impact of altered iron metabolism is still lacking. In addition, deficits in neuronal energy metabolism due to reduced glucose import were described for Alzheimer’s disease (AD) and its comorbidities like obesity, depression, cardiovascular disease, and type 2 diabetes mellitus. The aim of this review is to present the molecular link between both observations. Insufficient cellular glucose uptake triggers increased ferritin expression, leading to depletion of the cellular free iron pool and stabilization of the hypoxia-induced factor (HIF) 1α. This transcription factor induces the expression of the glucose transporters (Glut) 1 and 3 and shifts the cellular metabolism towards glycolysis. If this first line of defense is not adequate for sufficient glucose supply, further reduction of the intracellular iron pool affects the enzymes of the mitochondrial electron transport chain and activates the AMP-activated kinase (AMPK). This enzyme triggers the translocation of Glut4 to the plasma membrane as well as the autophagic recycling of cell components in order to mobilize energy resources. Moreover, AMPK activates the autophagic process of ferritinophagy, which provides free iron urgently needed as a cofactor for the synthesis of heme- and iron–sulfur proteins. Excessive activation of this pathway ends in ferroptosis, a special iron-dependent form of cell death, while hampered AMPK activation steadily reduces the iron pools, leading to hypoferremia with iron sequestration in the spleen and liver. Long-lasting iron depletion affects erythropoiesis and results in anemia of chronic disease, a common condition in patients with AD and its comorbidities. Instead of iron supplementation, drugs, diet, or phytochemicals that improve energy supply and cellular glucose uptake should be administered to counteract hypoferremia and anemia of chronic disease.

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COVID-19-induced neurological symptoms: focus on the role of metal ions

et al. 2023

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SARS-CoV-2-induced hypomethylation of the ferritin heavy chain (FTH1) gene underlies serum hyperferritinemia in severe COVID-19 patients

Cited by 7 publications

References 50 publications

SR2: Sparse Representation Learning for Scalable Single-cell RNA Sequencing Data Analysis

SR2: Sparse Representation Learning for Scalable Single-cell RNA Sequencing Data Analysis

Why Is Iron Deficiency/Anemia Linked to Alzheimer’s Disease and Its Comorbidities, and How Is It Prevented?

COVID-19-induced neurological symptoms: focus on the role of metal ions

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