Programmed cell death

Definition

Programmed cell death, or apoptosis, is a regulated process by which cells intentionally undergo death to maintain homeostasis and normal functioning within an organism. This mechanism is crucial for removing damaged, diseased, or unnecessary cells without causing harm to the surrounding tissues, playing a significant role in development, immune response, and overall cellular health.

5 Must Know Facts For Your Next Test

1. Apoptosis is characterized by distinct morphological changes such as cell shrinkage, chromatin condensation, and DNA fragmentation.
2. The process of programmed cell death can be triggered by internal signals (intrinsic pathway) like DNA damage or external signals (extrinsic pathway) such as death receptor activation.
3. Key players in apoptosis include Bcl-2 family proteins that regulate mitochondrial outer membrane permeabilization, affecting the release of cytochrome c into the cytoplasm.
4. Unlike necrosis, apoptosis is an orderly process that prevents inflammation and damage to surrounding tissues, making it critical for tissue homeostasis.
5. Defects in apoptotic pathways are linked to various diseases, including cancer, autoimmune disorders, and neurodegenerative diseases, highlighting its importance in health.

Review Questions

• How do intrinsic and extrinsic pathways differ in their mechanisms of inducing programmed cell death?
  • Intrinsic pathways of programmed cell death are initiated by internal signals such as DNA damage or oxidative stress that activate sensors like p53. This leads to mitochondrial changes, releasing factors like cytochrome c which activates caspases. In contrast, extrinsic pathways are triggered by external signals such as ligands binding to death receptors on the cell surface, directly activating caspases. Both pathways ultimately converge on common executioner caspases to carry out apoptosis.
• Discuss the role of Bcl-2 family proteins in the regulation of programmed cell death.
  • Bcl-2 family proteins are crucial regulators of apoptosis, consisting of both pro-apoptotic and anti-apoptotic members. Anti-apoptotic proteins like Bcl-2 and Bcl-xL help maintain mitochondrial integrity and prevent the release of pro-apoptotic factors. Conversely, pro-apoptotic proteins such as Bax and Bak promote mitochondrial outer membrane permeabilization, facilitating the apoptosome formation and activating caspases. The balance between these opposing forces determines whether a cell will undergo programmed cell death or survive.
• Evaluate the implications of dysregulation of programmed cell death in cancer development and treatment strategies.
  • Dysregulation of programmed cell death plays a significant role in cancer development; tumor cells often evade apoptosis by overexpressing anti-apoptotic proteins or mutating pro-apoptotic factors. This resistance to cell death contributes to uncontrolled proliferation and tumor survival. Understanding these mechanisms has led to innovative treatment strategies targeting apoptotic pathways, such as using BH3 mimetics to inhibit anti-apoptotic proteins or restoring p53 function. This highlights the critical need for therapies that can reinstate apoptosis in cancer cells to improve patient outcomes.

Related terms

Apoptosome: A large protein complex formed during apoptosis that activates initiator caspases, leading to the execution phase of cell death.

Caspases: A family of cysteine proteases that play essential roles in apoptosis by executing the death program and dismantling cellular structures.

Necrosis:

An uncontrolled form of cell death resulting from injury, infection, or other stressors that can lead to inflammation and damage to neighboring cells.