apoptotozie

Apoptotozie is a controlled form of programmed cell death that eliminates cells without provoking an inflammatory response. It is essential for normal development, tissue homeostasis, and immune regulation, and it helps remove cells that are damaged or pose a risk to the organism.

There are two main signaling pathways that trigger apoptosis: intrinsic (mitochondrial) and extrinsic (death receptor) pathways. The intrinsic pathway responds to cellular stress such as DNA damage, oxidative stress, or growth factor withdrawal. Mitochondrial outer membrane permeabilization releases cytochrome c, which forms a complex with Apaf-1 and procaspase-9 (the apoptosome) to activate downstream effector caspases (caspase-3, -6, -7). The process is tightly controlled by the Bcl-2 family of proteins, with anti-apoptotic members (e.g., Bcl-2, Bcl-xL) opposing pro-apoptotic members (e.g., Bax, Bak). The tumor suppressor p53 can promote intrinsic apoptosis in response to DNA damage by upregulating pro-apoptotic factors.

The extrinsic pathway is initiated by ligands binding to death receptors, such as Fas (CD95) or TNF receptor family members. This activates the death-inducing signaling complex (DISC) and caspase-8, which can directly activate effector caspases or amplify the mitochondrial pathway via Bid cleavage.

Execution of apoptosis leads to cell shrinkage, chromatin condensation, DNA fragmentation, membrane blebbing, and formation of apoptotic bodies that are cleared by phagocytes. Phosphatidylserine becomes exposed on the cell surface, signaling removal.

Dysregulation of apoptosis is implicated in many diseases: too little apoptosis can contribute to cancer, while excessive apoptosis is linked to neurodegenerative disorders. Therapies often aim to modulate apoptotic pathways to promote or inhibit this form of cell death.