CED9

CED-9, commonly written as ced-9, is a gene in the nematode Caenorhabditis elegans that encodes an anti-apoptotic member of the Bcl-2 protein family. The Ced-9 protein localizes to the outer mitochondrial membrane and promotes cell survival during development by inhibiting the caspase cascade that executes programmed cell death. The core apoptotic pathway in C. elegans involves the pro-death protein EGL-1 and the mitochondria-associated regulators CED-4 (the Apaf-1 homolog) and CED-3 (a caspase). Under normal conditions, Ced-9 binds and sequesters CED-4 at the mitochondria, preventing CED-4–mediated activation of CED-3. When a cell is destined to die, EGL-1 is expressed and binds to Ced-9, releasing CED-4 to activate CED-3 and trigger apoptosis. Through this mechanism, Ced-9 acts as a pivotal regulator of cell fate by integrating developmental and stress signals to control survival versus programmed cell death.

Genetic analyses show that loss-of-function mutations in ced-9 increase apoptosis, whereas gain-of-function mutations suppress it. Ced-9 is considered a functional homolog of mammalian Bcl-2 family proteins, highlighting the evolutionary conservation of the mitochondrial regulation of apoptosis. The study of ced-9 has contributed to understanding how mitochondrial signals influence cell fate decisions during development and how dysregulation of such pathways can affect organismal viability. See also: apoptosis in Caenorhabditis elegans, CED-3, CED-4, EGL-1.