Mechanisms and role of ferroptosis in disease [Jan. 17, 2023]

[Jul. 9, 2024] Previous Science Note

The field of ferroptosis research has grown exponentially in the past few years. This unique cell death by iron-dependent phospholipid peroxidation is regulated by multiple cellular metabolic pathways, including redox homeostasis, iron handling, mitochondrial activity, amino acid, lipid, and sugar metabolism, as well as various disease-related signaling pathways. Today, we introduce you to three highlighted articles focusing on iron resources, regulators, and the sensitive phenotype for ferroptosis in several diseases.

Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration
Click here for the original article: Sean K. Ryan, et al., Nature Neuroscience, 26, 12-26, 2023

Point of Interest

- iPS cell-derived tri-culture system that contains microglia, neurons, and astrocytes are used in this study

- Microglia grown in a tri-culture system are highly responsive to iron and susceptible to ferroptosis

- Iron overload causes a marked shift in the microglial transcriptional state 

- This microglial response contributes to neurodegeneration and is regulated by a novel ferroptosis susceptibility gene, SEC24B

Iron derived from autophagy-mediated ferritin degradation induces cardiomyocyte death and heart failure in mice
Click here for the original article: Jumpei Ito, et al., eLife, 10:e62174, 2021

Point of Interest

- Iron release from ferritin storage is through NCOA4-mediated autophagic degradation, known as ferritinophagy

- Deletion of Ncoa4 in mouse hearts improved cardiac function along with the attenuation of the upregulation of ferritinophagy-mediated ferritin degradation 4 weeks after pressure overload

- Free ferrous iron overload and increased lipid peroxidation were suppressed in NCOA4-deficient hearts

- Inhibition of lipid peroxidation significantly mitigated the development of pressure overload-induced dilated cardiomyopathy in wild-type mice

The MARCHF6 E3 ubiquitin ligase acts as an NADPH sensor for the regulation of ferroptosis
Click here for the original article: Kha The Nguyen, et al., Nature Cell Biology, 24, 1239-1251, 2022

Point of Interest

- The level of the anabolic reductant NADPH is a biomarker of ferroptosis sensitivity

- The transmembrane endoplasmic reticulum MARCHF6 E3 ubiquitin ligase recognizes NADPH through its C-terminal regulatory region

- This interaction upregulates the E3 ligase activity of MARCHF6, thus downregulating ferroptosis

- Inhibiting ferroptosis rescued the growth of MARCHF6-deficient tumours and peri-natal lethality of Marchf6–/– mice.

Related Techniques

Intracellular / mitochondrial ferrous ion (Fe2+) detection
FerroOrange(intracellular), Mito-FerroGreen(mitochondrial)
Lipid peroxidation detection
Liperfluo(intracellular), MitoPeDPP(mitochondrial)
Lipid Peroxidation Assay
Lipid Peroxidation Probe -BDP 581/591 C11-
Total ROS detection
Highly sensitive DCFH-DA or Photo-oxidation Resistant DCFH-DA
Mitochondrial superoxide detection
MitoBright ROS Deep Red - Mitochondrial Superoxide Detection
Mitochondrial membrane potential detection
JC-1 MitoMP Detection KitMT-1 MitoMP Detection Kit
Glutathione Quantification
GSSG/GSH Quantification Kit
Cystine Uptake detection
Cystine Uptake Assay Kit
MDA detection
MDA Assay Kit
Mitophagy or autophagy detection
Mitophagy Detection KitAutophagic Flux Assay Kit
Lysosomal function
Lysosomal Acidic pH Detection Kit -Green/Red and Green/Deep Red
Glycolysis/Oxidative phosphorylation Assay
 
Glycolysis/OXPHOS Assay Kit
 
Apoptosis detection in multiple samples
 
Annexin V Apoptosis Plate Assay Kit
 

Related Applications

Erastin-Induced Ferroptosis: Evaluating Intracellular Uptake and Redox Balance

We investigated the transition of cellular metabolisms in A549 cells treated with erastin, a known ferroptosis inducer. Our results revealed the following.

 

- The inhibition of cystine uptake by erastin led to a depletion of cysteine, which in turn increased the compensatory uptake of other amino acids.
- Glucose uptake, which typically promotes ferroptosis*, was found to decrease upon erastin treatment, suggesting a potential cellular self-defense mechanism.
- The depletion of cysteine resulted in a decrease in glutathione levels and an increase in Fe2+, ROS, and lipid peroxides, all of which are recognized markers of ferroptosis.


  Cell Line: A549
  Incubation Conditions: 100 μmol/l Erastin/MEM, 37℃, 3h
  *Reference: Xinxin Song, et al., Cell Reports, (2021)

Products in Use

① Amino Acid Uptake Amino Acid Uptake Assay Kit
② Glucose Uptake Glucose Uptake Assay Kit-Green
③ Cystine Uptake : Cystine Uptake Assay Kit
④ Intracellular glutathione GSSG/GSH Quantification Kit
⑤ Intracellular labile Fe FerroOrange
⑥ Intracellular total ROS ROS Assay Kit -Highly Sensitive DCFH-DA-
⑦ Lipid Peroxides Liperfluo

 

Product Classification

Product Classification