In-Depth Notes on Apoptosis and Cell Death

General Overview

  • Cell Death Types:
    • Apoptosis (programmed cell death)
    • Necrosis (non-programmed cell death)
    • Apoptosis is crucial for maintaining organismal health by regulating cell turnover.

Apoptosis Defined

  • Definition: Apoptosis is a controlled mechanism of cell deletion vital for the regulation of cell populations, acting in opposition to mitosis.
  • Morphological Features:
    • Active, programmed process with two main stages:
    1. Condensation of nucleus and cytoplasm, breaking down into membrane-bound apoptotic bodies.
    2. Apoptotic bodies are either shed or consumed by phagocytes for degradation.

Importance of Apoptosis

  • Roles in Development:
    • Involved in limb and organ formation during development.
    • Removal of unneeded structures, like the tail in tadpoles, regulated by thyroid hormones.
  • Elimination of Damaged Cells:
    • Targets cells with:
    • Irreparable organelle or DNA damage
    • Infections or cancerous cells.

Biochemical Markers of Apoptosis

  • Key Indicators:
    • DNA Cleavage: A hallmark of apoptosis.
    • Exposure of Phosphatidylserine (PS): Acts as an "eat me" signal to phagocytes.
    • Mitochondrial leakage: Loss of integrity leads to cytosolic release of cytochrome C, essential for apoptosis activation.

Caspases in Apoptosis

  • Caspases:
    • Initiator Caspases: Trigger apoptosis by activating downstream signals.
    • Executioner Caspases: Act on various cellular proteins to execute the death program.
    • Both types exist initially as inactive forms (procaspases) which are activated during apoptosis.

Pathways of Apoptosis Activation

  • Extrinsic Pathway:
    • Triggered by external signals through death receptors (e.g., TNF receptors).
  • Intrinsic Pathway:
    • Initiated by internal signals in response to stress (e.g., DNA damage), regulated by mitochondrial components like cytochrome C.

Regulation of Apoptosis

  • Bcl-2 Family Proteins:
    • Regulate the intrinsic pathway, controlling mitochondrial cytochrome C release.
    • Inhibitory Mechanisms:
    • Identify and inhibit pro-apoptotic proteins to prevent apoptosis.
  • Survival Factors:
    • External signals can inhibit apoptosis through various mechanisms, including upregulating anti-apoptotic proteins.

Consequences of Dysregulated Apoptosis

  • Too Much Apoptosis:
    • Can lead to tissue degenerations like heart attacks and strokes.
  • Too Little Apoptosis:
    • Results in diseases like cancer and autoimmune disorders, where abnormal cell proliferation occurs.
    • Cancer cells often harbor mutations in Bcl-2 and p53, facilitating survival despite damage.