Lecture: The Role of Mitochondria in Apoptosis

Overview of Mitochondria

• Primary Function: Known for metabolic pathways like the Krebs cycle and electron transfer chain that produce ATP.
• Energy Powerhouse: Commonly referred to as the cell's energy powerhouse.
• Other Function: Plays a significant role in apoptosis (programmed cell death).

Types of Cell Death

• Necrosis:
  • Uncontrolled cell death.
  • Response to extreme stress (e.g., trauma, infection).
• Apoptosis:
  • Controlled, programmed cell death.
  • Often confers advantages to the organism (e.g., development).
  • Example: Formation of fingers and toes through cell death in fetal development.

Factors Inducing Apoptosis

• DNA Damage:
  • Cells have repair mechanisms.
  • Extensive damage can trigger cell death to avoid passing on defective DNA.
• Infection:
  • Especially viral infections.
  • Immune cells recognize infected cells and induce apoptosis.
• Environmental Stress:
  • Deprivation of oxygen, nutrients, or cell-to-cell connections.
  • Lack of growth factors (hormones signaling cells to divide).
• Reactive Oxygen Species (ROS):
  • Include superoxide anion, hydroxide radical, hydrogen peroxide.
  • Result from oxygen's role in mitochondrial electron transfer chain.
  • Cells have enzymes and antioxidants to neutralize ROS.
  • Excess ROS can trigger apoptosis.

Mechanism of Apoptosis via Mitochondria

• BCL2 Family Proteins:
  • Regulate mitochondrial membrane permeability.
  • Two types: Pro-apoptotic (favoring apoptosis) and anti-apoptotic (inhibiting apoptosis).
• Cytochrome c Release:
  • Increased membrane permeability allows release of cytochrome c from intermembrane space into the cytoplasm.
  • Cytochrome c activates caspases (family of enzymes).

Role of Caspases

• Function of Caspases:
  • Proteases breaking down proteins after aspartate residue.
  • Activation by cytochrome c initiates a cascade effect.
  • Controls and orchestrates protein degradation.
  • Can activate nucleases (enzymes breaking down DNA).
• Distinct Feature: Apoptosis is caspase-mediated, unlike necrosis.
• Outcome: Degradation and recycling of cell components by surrounding cells.

Summary

• Apoptosis: Controlled cell death, conferring developmental and protective advantages.
• Mitochondria's Role: Central in initiating apoptosis through membrane permeability and caspase activation.