Intrinsic pathway

Definition

The intrinsic pathway refers to a specific signaling cascade that triggers apoptosis, or programmed cell death, within a cell. This pathway is activated in response to internal signals such as DNA damage or cellular stress, leading to the activation of caspases, which are crucial enzymes that execute the cell death program. The intrinsic pathway is a critical component of cell cycle regulation and plays a significant role in maintaining cellular homeostasis by eliminating damaged or unwanted cells.

5 Must Know Facts For Your Next Test

1. The intrinsic pathway is primarily initiated by signals such as DNA damage, oxidative stress, or developmental cues, which are detected within the cell.
2. Mitochondrial outer membrane permeabilization (MOMP) is a critical step in the intrinsic pathway that leads to the release of pro-apoptotic factors like cytochrome c into the cytoplasm.
3. Once cytochrome c is released, it binds to Apaf-1 and activates caspase-9, which then activates downstream effector caspases such as caspase-3.
4. Bcl-2 family proteins play a pivotal role in determining whether a cell will undergo apoptosis by regulating MOMP; anti-apoptotic members prevent apoptosis, while pro-apoptotic members promote it.
5. The intrinsic pathway is essential for normal development and tissue homeostasis, ensuring that damaged or superfluous cells are eliminated to prevent diseases like cancer.

Review Questions

• How does the intrinsic pathway relate to cellular responses to DNA damage?
  • The intrinsic pathway is closely linked to cellular responses to DNA damage because it is activated when cells detect internal stress signals. When DNA damage occurs, signaling mechanisms are triggered that can lead to mitochondrial dysfunction and the release of pro-apoptotic factors. This ultimately activates caspases through the intrinsic apoptotic cascade, resulting in programmed cell death to prevent damaged cells from proliferating.
• Discuss the role of Bcl-2 family proteins in regulating the intrinsic pathway of apoptosis.
  • Bcl-2 family proteins play a critical role in regulating the intrinsic pathway by controlling mitochondrial outer membrane permeabilization. Anti-apoptotic proteins, like Bcl-2 itself, inhibit apoptosis by preventing MOMP and keeping cytochrome c sequestered within mitochondria. Conversely, pro-apoptotic members such as Bax promote MOMP, leading to cytochrome c release and subsequent activation of caspases. The balance between these opposing forces determines whether a cell will undergo apoptosis or survive.
• Evaluate the significance of mitochondrial involvement in the intrinsic pathway and its implications for therapeutic strategies targeting cancer.
  • Mitochondria are central to the intrinsic pathway due to their role in releasing factors like cytochrome c that activate apoptosis. This involvement highlights how targeting mitochondrial function could serve as an effective therapeutic strategy against cancer. By enhancing the pro-apoptotic signals or inhibiting anti-apoptotic factors within cancer cells, therapies could push these cells toward programmed death. Understanding this mechanism allows researchers to develop drugs that selectively induce apoptosis in cancerous cells while sparing healthy ones, thereby improving treatment outcomes.

Related terms

Caspases: A family of cysteine proteases that play essential roles in apoptosis, inflammation, and cell differentiation, with caspase-3 being one of the key executioner caspases in the intrinsic pathway.

Mitochondria: Organelles known as the powerhouses of the cell that are involved in energy production and play a central role in the intrinsic pathway by releasing cytochrome c to activate apoptosis.

Bcl-2 Family Proteins: A group of proteins that regulate apoptosis by either promoting cell survival (anti-apoptotic) or triggering cell death (pro-apoptotic), influencing the intrinsic pathway's decision-making process.