What is the Difference Between Apoptosis Ferroptosis and Pyroptosis

The key difference between apoptosis ferroptosis and pyroptosis is their triggers. Apoptosis is typically triggered by abnormal cell growth or damage to cellular DNA. In contrast, ferroptosis is triggered by the consequences of lethal lipid peroxidation, which results from an iron-dependent accumulation of reactive oxygen species. Pyroptosis, on the other hand, is triggered by the primary response of the cell to infectious organisms.

Programmed cell death is the death of a cell due to the events inside of a cell. It is triggered by an initiator or signalling phase followed by an effector stage that results in cell death. Apoptosis, ferroptosis, and pyroptosis are all forms of programmed cell death that activate genes and molecules inside the cell.

CONTENTS

1. Overview and Key Difference
2. What is Apoptosis  
3. What is Ferroptosis  
4. What is Pyroptosis
5. Similarities – Apoptosis Ferroptosis and Pyroptosis
6. Apoptosis vs. Ferroptosis vs. Pyroptosis in Tabular Form
7. Summary – Apoptosis vs. Ferroptosis vs. Pyroptosis

What is Apoptosis?

Apoptosis is one of the earliest types of programmed cell death discovered. It is also known as cell suicide. It is triggered by abnormal cell growth or damage in cellular DNA. In this mechanism, signal molecules activate genes within the cell that cause the cell to commit apoptosis.

The best example is the tp53 protein, which is a tumor suppressor. Tp53 causes cells to commit apoptosis when it detects that cells are dividing too quickly. This process prevents tumors and abnormal cell growth. Furthermore, in this mechanism, the cell releases proteases, which break bonds between proteins. Therefore, proteases cause the cell membrane to disintegrate and DNA to condense and break up. Later, the material inside the cell is released in small membrane-bound capsules called apoptotic bodies, while phagocytes engulf and dispose of these apoptotic bodies at the end of the process.

What is Ferroptosis?

Ferroptosis is a regulated cell death triggered by consequences of lethal lipid peroxidation arising from an iron-dependent reactive oxygen species (ROS) accumulation. Ferroptic cells usually have ruptured cell membranes, and they release their intracellular contents. Moreover, ferroptosis can also be triggered by the loss or decreased activity of Glutathione peroxidase 4 (GPX4). This is because GPX4 is an enzyme that reduces hydrogen peroxide, organic hydroperoxides, and lipid peroxide.

In the absence of GPX4, there is uncontrolled lipid peroxidation due to the accumulation of lipid radicals and lipid peroxy radicals. Lipid peroxidation changes the chemistry of lipids. This alters cellular membranes and can result in loss of cell membrane integrity and cell death. However, ferroptosis can be suppressed by iron chelators, lipophilic antioxidants, and inhibitors of lipid peroxidation.

What is Pyroptosis?

Pyroptosis is a type of programmed cell death that is triggered by the primary response of the cell to infectious organisms. The immune system of the body controls it. Pyroptosis is activated by an enzyme called caspase-1.

In this mechanism, caspase-1 activates proteins that induce an immune response from the cell. This immune response causes the cell to lyse. Later, the cell membrane bursts out, and the contents of the cell spill out of the cell. The released DAMPs from the ruptured cell further trigger more inflammation and a larger immune response from surrounding cells and organs in pyroptosis.

What are the Similarities Between Apoptosis Ferroptosis and Pyroptosis?

• Apoptosis, ferroptosis, and pyroptosis are all forms of programmed cell death.
• All these mechanisms activate genes and molecules inside the cell.
• They are triggered by an initiator, followed by an effector stage.
• The deregulation of these mechanisms can lead to cancer growth.

What is the Difference Between Apoptosis Ferroptosis and Pyroptosis?

Apoptosis is a type of programmed cell death triggered by abnormal cell growth or damage in cellular DNA, while ferroptosis is a type of programmed cell death triggered by consequences of lethal lipid peroxidation arising from an iron-dependent reactive oxygen species (ROS) accumulation. On the other hand, pyroptosis is a type of programmed cell death triggered by the primary response of the cell to infectious organisms. Thus, this is the key difference between apoptosis ferroptosis and pyroptosis. Furthermore, apoptosis is induced by proteins like tp53 protein, a tumor suppressor, whereas ferroptosis is induced by enzymes like glutathione peroxidase 4 (GPX4), and pyroptosis is induced by enzymes like caspase-1.

The infographic below presents the differences between apoptosis ferroptosis and pyroptosis in tabular form for side-by-side comparison.

Summary – Apoptosis vs. Ferroptosis vs. Pyroptosis

Programmed cell death plays an important role in animal development and tissue homeostasis. Abnormal regulation of these processes is associated with a wide variety of human diseases, including immunological disorders, developmental disorders, neurodegeneration, and different cancers. Apoptosis, ferroptosis, and pyroptosis are all forms of programmed cell death. Apoptosis is triggered by abnormal cell growth or damage in cellular DNA, whereas ferroptosis is triggered by the consequence of lethal lipid peroxidation arising from an iron-dependent reactive oxygen species (ROS) accumulation, and pyroptosis is triggered by the primary response of the cell to infectious organisms. So, this summarizes the difference between apoptosis ferroptosis and pyroptosis.

Reference:

1. “Apoptosis.” Genome.Gov.
2. Yan, Hong-fa, et al. “Ferroptosis: Mechanisms and Links with Diseases.” Nature News, Nature Publishing Group.
3. “Pyroptosis – An Overview.” ScienceDirect.

Image Courtesy:

1. “Apoptotic cell disassembly” By Aaron Smith, Michael AF Parkes, Georgia K Atkin-Smith, Rochelle Tixeira, Ivan KH Poon – Wikiversity:Draft: WikiJournal of Medicine/Cell disassembly during cell death (CC BY 4.0) via Commons Wikimedia
2. “Ferroptosis human prostate cancer model” By Evilonan – Own work (CC BY-SA 4.0) via Commons Wikimedia
3. “Pyroptosis pathways” (CC BY-SA 4.0) via Commons Wikimedia