positive regulation of mitochondrial membrane permeability involved in apoptotic process

Definition

Target type: biologicalprocess

Any positive regulation of mitochondrial membrane permeability that is involved in apoptotic process. [GOC:mtg_apoptosis, GOC:pm, GOC:TermGenie, PMID:19168129]

Positive regulation of mitochondrial membrane permeability involved in apoptotic process is a crucial step in the programmed cell death pathway. It involves a tightly regulated cascade of events that lead to the release of pro-apoptotic factors from the mitochondria into the cytosol, ultimately triggering the execution of cell death.

The mitochondrial outer membrane (MOM) acts as a gatekeeper, maintaining a delicate balance between life and death signals. Under normal conditions, the MOM is impermeable to apoptogenic proteins residing within the intermembrane space (IMS), such as cytochrome c, Smac/DIABLO, and AIF. However, during apoptosis, the MOM undergoes a dramatic permeabilization, allowing these proteins to escape into the cytosol.

Several mechanisms contribute to the positive regulation of MOM permeability:

1. **Mitochondrial Permeability Transition Pore (mPTP) Opening:** The mPTP is a large, non-selective channel formed by the interaction of several proteins in the MOM, including the voltage-dependent anion channel (VDAC), adenine nucleotide translocator (ANT), and cyclophilin D. In response to stress signals, such as oxidative stress or calcium overload, the mPTP can open, disrupting the mitochondrial membrane potential and leading to the release of IMS contents.

2. **Activation of Pro-apoptotic Bcl-2 Family Members:** The Bcl-2 family of proteins plays a central role in regulating MOM permeability. Pro-apoptotic members, such as Bax and Bak, promote MOM permeabilization, while anti-apoptotic members, such as Bcl-2 and Bcl-xL, inhibit it. Upon apoptotic stimuli, pro-apoptotic Bcl-2 proteins undergo conformational changes, oligomerize, and insert into the MOM, forming pores that allow the passage of pro-apoptotic factors.

3. **Disruption of Mitochondrial Membrane Integrity:** Other mechanisms, including the activation of caspases and the accumulation of reactive oxygen species (ROS), can directly damage the MOM, increasing its permeability.

The release of cytochrome c from the mitochondria into the cytosol is a key event in the apoptotic cascade. Cytochrome c binds to apoptotic protease-activating factor 1 (Apaf-1), which then recruits pro-caspase-9 to form the apoptosome. The apoptosome activates caspase-9, initiating a cascade of caspase activation that ultimately leads to the dismantling of the cell.

In summary, positive regulation of mitochondrial membrane permeability is a complex and tightly regulated process involving a network of proteins and signaling pathways. This critical step in apoptosis ensures the efficient and controlled elimination of damaged or unwanted cells, maintaining tissue homeostasis and preventing uncontrolled cell growth.'
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Proteins (2)

Compounds (33)