Intrinsic pathway

Definition

The intrinsic pathway is a crucial series of molecular events that trigger apoptosis, or programmed cell death, within cells. It primarily involves the activation of caspases, which are proteolytic enzymes that play a key role in dismantling cellular components. This pathway is often initiated by internal cellular stressors such as DNA damage or oxidative stress, linking it to various cellular responses and disease mechanisms.

5 Must Know Facts For Your Next Test

1. The intrinsic pathway is often activated in response to severe cellular stress, such as irreparable DNA damage or significant oxidative stress.
2. Key players in the intrinsic pathway include mitochondrial proteins like cytochrome c, which when released into the cytosol activate caspases.
3. This pathway is tightly regulated by Bcl-2 family proteins, which can either promote survival or trigger apoptosis depending on the signals received.
4. Dysregulation of the intrinsic pathway is linked to various diseases, including cancer, where evasion of apoptosis allows for uncontrolled cell proliferation.
5. The intrinsic pathway can be distinguished from the extrinsic pathway, which is activated by external signals from death receptors on the cell surface.

Review Questions

• How does the intrinsic pathway of apoptosis relate to cellular stress and what mechanisms initiate its activation?
  • The intrinsic pathway is directly linked to cellular stress, as it often gets activated due to factors like DNA damage or oxidative stress. When cells experience these types of stress, they trigger signaling cascades that lead to mitochondrial dysfunction. This results in the release of pro-apoptotic factors like cytochrome c into the cytosol, which activates caspases and ultimately leads to programmed cell death.
• Discuss the role of Bcl-2 family proteins in regulating the intrinsic pathway and how their balance can influence cell fate.
  • Bcl-2 family proteins play a pivotal role in determining whether a cell undergoes apoptosis via the intrinsic pathway. These proteins can be classified as pro-apoptotic or anti-apoptotic. Pro-apoptotic members promote cell death by facilitating mitochondrial membrane permeabilization, while anti-apoptotic members inhibit this process. The balance between these opposing forces influences whether a cell survives under stress or initiates apoptosis, highlighting their importance in cellular homeostasis and disease mechanisms.
• Evaluate the significance of understanding the intrinsic pathway in the context of therapeutic approaches for diseases such as cancer.
  • Understanding the intrinsic pathway is crucial for developing targeted therapies in diseases like cancer, where apoptosis is often disrupted. By manipulating components of this pathway, such as enhancing pro-apoptotic signals or inhibiting anti-apoptotic signals, new treatments can potentially restore normal apoptotic processes in cancer cells. This therapeutic strategy aims to make cancer cells more susceptible to programmed cell death, overcoming their resistance and leading to more effective treatment outcomes.

Related terms

Caspases: Caspases are a family of cysteine proteases that execute apoptosis by cleaving specific substrates, leading to cellular disassembly.

Mitochondria: Mitochondria are organelles that play a central role in energy production and are also involved in initiating the intrinsic pathway by releasing cytochrome c.

Bcl-2 family proteins: These proteins regulate apoptosis by either promoting or inhibiting the intrinsic pathway, influencing cell survival or death.