Slide 1 - AccessCardiology
... Apoptosis pathway. Two distinct, but not mutually exclusive, pathways of apoptotic cell death have been well desribed: extrinsic and intrinsic pathways. In the extrinsic pathway, soluble or cell surface death ligands, such as TNF-α and Fas ligand, bind to the corresponding death receptors inducing a ...
... Apoptosis pathway. Two distinct, but not mutually exclusive, pathways of apoptotic cell death have been well desribed: extrinsic and intrinsic pathways. In the extrinsic pathway, soluble or cell surface death ligands, such as TNF-α and Fas ligand, bind to the corresponding death receptors inducing a ...
Outline --- Programmed Cell Death 1. Apoptosis An overview: the
... An overview: the establishment of the concept/field Morphological observations (concept/hypothesis) Medicine/cancer (Bcl-2, the founder of a new class of oncogene) Basic research (proof of the concept by C. elegans genetics) In-depth discussion of certain topics Mitochondria-mediated caspase act ...
... An overview: the establishment of the concept/field Morphological observations (concept/hypothesis) Medicine/cancer (Bcl-2, the founder of a new class of oncogene) Basic research (proof of the concept by C. elegans genetics) In-depth discussion of certain topics Mitochondria-mediated caspase act ...
No Slide Title
... the common pathway of apoptosis. Upon PT, apoptogenic factors leak into the cytoplasm from the mitochondrial intermembrane space. Two such factors, cytochrome c and apoptosis inducing factor (AIF), begin a cascade of proteolytic activity that ultimately leads to nuclear damage (DNA fragmentation, DN ...
... the common pathway of apoptosis. Upon PT, apoptogenic factors leak into the cytoplasm from the mitochondrial intermembrane space. Two such factors, cytochrome c and apoptosis inducing factor (AIF), begin a cascade of proteolytic activity that ultimately leads to nuclear damage (DNA fragmentation, DN ...
Apoptosome
The apoptosome is a large quaternary protein structure formed in the process of apoptosis. Its formation is triggered by the release of cytochrome c from the mitochondria in response to an internal (intrinsic) or external (extrinsic) cell death stimulus. Stimuli can vary from DNA damage and viral infection to developmental cues such as those leading to the degradation of a tadpole's tail.In mammalian cells, once cytochrome c is released, it binds to the cytosolic protein Apaf-1 to facilitate the formation of apoptosome. An early biochemical study suggests a two-to-one ratio of cytochrome c to apaf-1 for apoptosome formation. However, recent structural studies suggest the cytochrome c to apaf-1 ratio is one-to-one. It has also been shown that the nucleotide dATP as third component binds to apaf-1, however its exact role is still debated. The mammalian apoptosome had never been crystallized, but a human APAF-1/cytochrome-c apoptosome has been imaged at lower (2 nm) resolution by cryogenic transmission electron microscopy 10 years ago, revealing a wheel-like particle with 7-fold symmetry. Recently, a medium resolution (9.5 Ångström) structure of human apoptosome was also solved by cryo-electron microscopy, which allows unambiguous inference for positions of all the APAF-1 domains (CARD, NBARC and WD40) and cytochrome c. There is also now a crystal structure of the monomeric, inactive Apaf-1 subunit (PDB 3SFZ). Once formed, the apoptosome can then recruit and activate the inactive pro-caspase-9. Once activated, this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis.