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The stoichiometry of cytochrome c to Apaf-1 within the complex is proved to be 1:1. [1] There are some debates about whether stable incorporation of cytochrome c into the apoptosome is required following oligomerization, but recent structural data favor the idea that cytochrome c stabilizes the oligomeric human apoptosome. [1]
Cytochrome c was also discovered in 1996 by Xiaodong Wang to have an intermediate role in apoptosis, a controlled form of cell death used to kill cells in the process of development or in response to infection or DNA damage. [21] Cytochrome c binds to cardiolipin in the inner mitochondrial membrane, thus anchoring its presence and keeping it ...
Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. The apoptosome binds and cleaves Procaspase-9 protein, releasing its mature, activated form. The precise mechanism for this reaction is still debated though work published by Guy Salvesen suggests that the apoptosome may induce caspase-9 dimerization and subsequent ...
Caspase-9 is an enzyme that in humans is encoded by the CASP9 gene.It is an initiator caspase, [5] critical to the apoptotic pathway found in many tissues. [6] Caspase-9 homologs have been identified in all mammals for which they are known to exist, such as Mus musculus and Pan troglodytes.
Small soluble cytochrome c proteins with a molecular weight of 8-12 kDa and a single heme group belong to class I. [10] [11] It includes the low-spin soluble cytC of mitochondria and bacteria, with the heme-attachment site located towards the N-terminus, and the sixth ligand provided by a methionine residue about 40 residues further on towards the C-terminus.
When inhibiting caspase-3 and caspase-7 activity, the BIR2 domain of XIAP binds to the active-site substrate groove, blocking access of the normal protein substrate that would result in apoptosis. [13] [14] Caspases are activated by cytochrome c, which is released into the cytosol by dysfunctioning mitochondria. [7]
The X-linked inhibitor of apoptosis protein is overexpressed in cells of the H460 cell line. XIAPs bind to the processed form of caspase-9 and suppress the activity of apoptotic activator cytochrome c, therefore overexpression leads to a decrease in the number of proapoptotic agonists. As a consequence, the balance of anti-apoptotic and ...
Apoptosis inducing factor is involved in initiating a caspase-independent pathway of apoptosis (positive intrinsic regulator of apoptosis) by causing DNA fragmentation and chromatin condensation. Apoptosis inducing factor is a flavoprotein. [2] It also acts as an NADH oxidase. Another AIF function is to regulate the permeability of the ...