ApoptoseSignalwegen

ApoptoseSignalwegen refers to the cellular signaling pathways that regulate apoptosis, a controlled form of programmed cell death essential for development and maintaining cellular homeostasis. The best characterized routes are the intrinsic (mitochondrial) pathway and the extrinsic (death receptor) pathway, both converging on a cascade of proteolytic enzymes called caspases that dismantle the cell in an orderly manner.

The intrinsic pathway is driven by cellular stress such as DNA damage, oxidative stress, or nutrient deprivation. These signals alter the balance of BCL-2 family proteins, leading to mitochondrial outer membrane permeabilization (MOMP). This releases cytochrome c into the cytoplasm, where it participates in forming the apoptosome with Apaf-1 and procaspase-9, activating caspase-9. Caspase-9 then activates executioner caspases like caspase-3 and caspase-7, which drive cellular dismantling. Regulators include pro-apoptotic Bax and Bak, anti-apoptotic BCL-2 and BCL-xL, inhibitors of apoptosis (IAPs), and the mitochondrial protein SMAC/DIABLO which can antagonize IAPs.

The extrinsic pathway is initiated by extracellular signals binding to death receptors such as Fas (CD95) or TNF receptor family members (DR4/DR5). Ligand binding recruits adaptor proteins and activates initiator caspases, particularly caspase-8 or caspase-10. Caspase-8 can directly activate executioner caspases or, in many cells, cleave Bid to tBid, linking to the intrinsic pathway to amplify the death signal.

The execution phase leads to systematic cleavage of cellular substrates, DNA fragmentation, membrane changes, and the characteristic morphological features of apoptosis. Dysregulation of ApoptoseSignalwegen is implicated in cancer, neurodegenerative diseases, and immune disorders, making it a key focus of therapeutic research.