Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.

Apoptosis

Apoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound apoptotic bodies form. At the molecular level, key molecules involved in apoptosis include caspases, BAX, other BCL-2 family proteins, and cytochrome c. BCL-2 family proteins regulate pro- and anti-apoptotic signaling. BAX, in particular, promotes mitochondrial membrane permeabilization, leading to the release of cytochrome. Cytochrome c then activates caspases, which function as executioner enzymes that dismantle the cell.

Phagocytes efficiently clear these bodies without causing inflammation. Apoptosis plays a role in embryonic development, hormone withdrawal, immune control, and responses to viral infections. It can be triggered by severe cellular injury, endoplasmic reticulum (ER) stress, or caspase activation via intrinsic and extrinsic pathways. When not adequately regulated, apoptosis contributes to diseases such as cancer and autoimmune disorders.

Autophagy

Autophagy supports cell survival by breaking down and recycling damaged components. The process begins with the formation of a phagophore, which expands into an autophagosome that later fuses with a lysosome for digestion. Autophagy maintains metabolism during starvation, clears damaged organelles, and supports overall cell quality control.