Ferroptosis as a New Type of Inflammatory Programmed Cell Death

Bryent Lee

Bryent Lee
Nov 12, 2020 1:00:00 PM

When it comes to programmed cell death (PCD), apoptosis is usually the first process that comes to mind. However, there is a new type of inflammatory PCD discovered in 2012, known as ferroptosis, that is genetically and biochemically distinct from other PCD.1

 

It is usually accompanied by a significant amount of iron accumulation and lipid peroxidation during the cell death process. Oxidative cell death occurs when there is a decrease in antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) affected by the ferroptosis-inducing factors. Recent studies have shown that ferroptosis is closely related to the pathophysiological processes of many diseases such as acute kidney injury, blood diseases, tumors, and neurological diseases as shown below in Figure 1:

 

 

Ferroptosis Role in Disease

 Figure 1. The role of ferroptosis in multiple system diseases (Source).

 

 Activating or blocking the ferroptosis pathway has proved to be a promising strategy to alleviate progression of numerous diseases. Therefore, the specific molecular mechanisms and functional changes of ferroptosis should be further examined for the development of related diseases. Let’s take a closer look at the main mechanisms of ferroptosis.

 

Mechanism of Ferroptosis

Morphologically, ferroptosis occurs mainly in cells as reduced mitochondrial volume, increased bilayer membrane density, and reduction or disappearance of mitochondrial cristae; but the cell membrane remains intact, the nucleus is normal in size, and there is no concentration of chromatin. Biologically, ferroptosis sensitivity is modulated by 4 main mechanisms as illustrated in Figure 2 below:1

 

Ferroptosis

Figure 2. Regulatory pathways of ferroptosis (Source)

 

A) The regulation of glutathione (GSH) and redox homeostasis, such as function of system xc-, glutathione peroxidase 4 (GPX4) regulation, FSP1-CoQ10- NAD(P)H pathway, sulfur transfer pathway, mevalonate (MVA) pathway, glutamine metabolic pathway, NRF2 and p53 regulatory axis.

B) The regulation of iron homeostasis, such as the regulation of ATG5-ATG7-NCOA4 pathway, IREB regulation system, and the regulatory pathways of heat shock proteins.

C) Related enzymes around glucose and lipid metabolism, such as PHGDH, G6PD, ACSL4, and LPCAT3, etc.

D) Mitochondria function regulation, such as voltage-dependent anion channels (VDACs), mitochondrial electron transport chain (ETC), TCA cycle, and glutaminolysis.

 

The most common regulation of ferroptosis is achieved through mechanism A above. System xc- provides the exchange of cysteine and glutamate in and out of the cell. Cysteine that is in the cells is involved in the synthesis of glutathione (GSH) and works to reduce ROS and reactive nitrogen together with GPX4. While P53 can inhibit the system xc- uptake of cysteine and RSL3 can inhibit GPX4, both inhibitions can lead to the accumulation of lipid ROS and eventually induce ferroptosis.2

 

After examining the mechanism and understanding the pathways involved in the process, it’s important to note that ABclonal offers several ferroptosis antibodies in our catalog, for use in multiple areas of research as shown in the table below:

 

Ferroptosis Research Products at ABclonal

Category

Key Target

Catalog No.

Product Name

Application

Iron Uptake and Export

TfR1

A5865

TFRC Rabbit pAb

WB,IHC,IF

Iron Storage

FTL

A11241

Ferritin Light Chain mAb

WB, IHC

Anti-Ferroptosis

Redox Regulation

HO-1

A19062

Heme Oxygenase 1 Rabbit mAb

WB, IHC 

GPX4

A11243

GPX4 Rabbit mAb

WB, IHC 

NRF2

A11159

NRF2 Rabbit pAb

WB,IHC,IF

NQO1 

A19586

NQO1 Rabbit mAb

WB, IHC 

Pro-Ferroptosis

Redox Regulation

PEBP1

A12768

PEBP1 Rabbit mAb

WB

DPP4/CD26

A4252

CD26 Rabbit mAb

WB

NOXs 

A19701

NOX2/CYBB/gp91phox Rabbit mAb

WB

Ferritinophagy

NCOA4

A5695

[KO Validated] NCOA4 Rabbit pAb

WB,IHC,IF 

 

**All product listed above have human, mouse and rat reactivity.

**Additional related antibodies not shown in the table above can be found here.

 


References

  1. Li, Jie, et al. “Ferroptosis: Past, Present and Future.” Cell Death & Disease, vol. 11, no. 2, 2020, doi:10.1038/s41419-020-2298-2.
  2. Cao, Jennifer Yinuo, and Scott J. Dixon. “Mechanisms of Ferroptosis.” Cellular and Molecular Life Sciences, vol. 73, no. 11-12, 2016, pp. 2195–2209., doi:10.1007/s00018-016-2194-1.

 

 

Tags: Apoptosis, Research, inflammation, Ferroptosis, programmed cell death