apoptotic

Apoptotic refers to apoptosis, a controlled form of programmed cell death that enables development, maintenance of cellular homeostasis, and removal of damaged cells. Characteristic features include cell shrinkage, chromatin condensation, DNA fragmentation, membrane blebbing, and formation of apoptotic bodies that are cleared by phagocytes, often without triggering inflammation.

The intrinsic or mitochondrial pathway is activated by cellular stress such as DNA damage, oxidative stress, or growth factor deprivation. It is regulated by BCL-2 family proteins that control mitochondrial outer membrane permeabilization. Release of cytochrome c into the cytoplasm leads to apoptosome assembly with APAF1 and procaspase-9, activating effector caspases like caspase-3, caspase-6, and caspase-7 to execute cell death.

The extrinsic or death receptor pathway is initiated by ligands such as Fas ligand or TRAIL binding to death receptors (for example Fas/CD95, TRAIL receptors) on the cell surface. This triggers the formation of the DISC and activation of initiator caspases, primarily caspase-8 or caspase-10, which in turn activate effector caspases or amplify the intrinsic pathway via Bid cleavage.

Apoptosis is tightly regulated by caspases, inhibitors of apoptosis proteins (IAPs), and the p53 tumor suppressor, which can promote apoptosis in response to DNA damage by upregulating pro-apoptotic BCL-2 family members such as BAX and BAK. Balance between pro- and anti-apoptotic signals determines cell fate.

Proper apoptosis shapes organ development, maintains tissue homeostasis, and eliminates damaged or potentially dangerous cells. Dysregulation is linked to disease: insufficient apoptosis contributes to cancer and autoimmune conditions, while excessive apoptosis is observed in neurodegenerative disorders and ischemic injury. Detection methods include TUNEL assays and Annexin V staining of phosphatidylserine exposure on early apoptotic cells.