Apoptosis: Programmed Cell Death

Biochemical Pathways Involved in Apoptosis

Apoptosis is a tightly regulated process of programmed cell death essential for maintaining cellular homeostasis and eliminating damaged or unnecessary cells. It involves a cascade of biochemical events leading to characteristic morphological changes and ultimate cell disposal.

Intrinsic Pathway

The intrinsic pathway, or mitochondrial pathway, is triggered by intracellular stress such as DNA damage or oxidative stress. It involves:

• Activation of pro-apoptotic Bcl-2 family proteins (e.g., Bax, Bak)
• Release of cytochrome c from mitochondria
• Formation of the apoptosome, activating caspase-9
• Sequential activation of caspase-3, leading to cell dismantling

Extrinsic Pathway

The extrinsic pathway is initiated by external signals via death receptors (e.g., Fas, TNF receptor). Steps include:

• Binding of ligands (e.g., FasL, TNF-α)
• Recruitment of FADD and activation of caspase-8
• Direct activation of caspase-3 or amplification via Bid cleavage
• Execution of apoptosis via proteolytic cleavage of cellular components

Regulation and Implications

Apoptosis is tightly controlled by regulatory proteins such as p53, Bcl-2, and IAPs. Dysregulation can lead to diseases such as cancer (reduced apoptosis) or neurodegenerative disorders (excess apoptosis). Therapeutic interventions targeting apoptotic pathways offer promising strategies for treating various conditions.