intrinsic apoptotic signaling pathway in response to hydrogen peroxide

Definition

Target type: biologicalprocess

The series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway is induced in response to hydrogen peroxide (H2O2). [GOC:bf, GOC:PARL]

Hydrogen peroxide (H2O2), a reactive oxygen species (ROS), can induce intrinsic apoptosis by activating the mitochondrial pathway. This pathway is characterized by the release of pro-apoptotic proteins from the mitochondria into the cytoplasm, ultimately leading to the activation of caspases and cell death.

Here's a detailed breakdown of the process:

**1. H2O2-induced stress and mitochondrial damage:**

* H2O2 can directly damage mitochondrial proteins and lipids, leading to increased mitochondrial membrane permeability.
* The accumulation of ROS, including H2O2, can also trigger the formation of reactive nitrogen species (RNS), which further contribute to mitochondrial dysfunction.

**2. Activation of pro-apoptotic proteins:**

* H2O2-induced stress can activate the Bcl-2 family of proteins, specifically the pro-apoptotic members Bax and Bak.
* These proteins translocate to the mitochondrial outer membrane, where they oligomerize and form pores.

**3. Release of cytochrome c and other pro-apoptotic factors:**

* The formation of Bax/Bak pores allows the release of cytochrome c and other pro-apoptotic factors, such as Smac/DIABLO and AIF, from the mitochondrial intermembrane space into the cytoplasm.

**4. Formation of the apoptosome:**

* Cytochrome c binds to the adaptor protein Apaf-1, which then recruits pro-caspase-9.
* This complex, known as the apoptosome, activates caspase-9.

**5. Caspase cascade activation:**

* Activated caspase-9, an initiator caspase, activates downstream executioner caspases, including caspase-3 and caspase-7.

**6. Execution of apoptosis:**

* Activated executioner caspases cleave various cellular substrates, leading to the dismantling of the cell's structure and function. This includes:
* DNA fragmentation
* Nuclear envelope breakdown
* Cell shrinkage
* Formation of apoptotic bodies

**7. Phagocytosis of apoptotic cells:**

* Apoptotic cells display "eat me" signals that attract phagocytes, which engulf and remove the dying cells, preventing inflammation.

The intrinsic apoptotic pathway triggered by H2O2 is a tightly regulated process that involves a complex interplay of proteins and signaling pathways. This process is essential for maintaining cellular homeostasis and removing damaged or unwanted cells.'
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Proteins (2)

Compounds (144)