Apoptosome

Human apoptosome CARD complex

Human apoptosome CARD complex
Apoptosome atomic model

Apoptosome atomic model
Apoptosome surface rendering

Apoptosome surface rendering
Apoptosomes

Apoptosomes

Apoptosome[edit]

The apoptosome is a large quaternary protein structure formed in the process of apoptosis, or programmed cell death. It plays a crucial role in the intrinsic pathway of apoptosis by activating caspase enzymes, which are responsible for the execution phase of cell death.

Structure[edit]

The apoptosome is typically composed of several molecules of Apaf-1, cytochrome c, and ATP or dATP. In humans, the apoptosome is a heptameric complex, meaning it consists of seven Apaf-1 molecules. Each Apaf-1 molecule contains several domains, including a caspase recruitment domain (CARD), a nucleotide-binding oligomerization domain (NOD), and a series of WD40 repeats.

Formation[edit]

The formation of the apoptosome is initiated by the release of cytochrome c from the mitochondria into the cytosol. This release is often triggered by cellular stress or damage signals. Once in the cytosol, cytochrome c binds to Apaf-1, causing a conformational change that allows Apaf-1 to bind ATP or dATP. This binding promotes the oligomerization of Apaf-1 into the heptameric apoptosome structure.

Function[edit]

The primary function of the apoptosome is to activate caspase-9, an initiator caspase. The CARD domain of Apaf-1 interacts with the CARD domain of procaspase-9, facilitating its recruitment to the apoptosome. Once bound, procaspase-9 undergoes autocatalytic cleavage to become active caspase-9. Active caspase-9 then cleaves and activates downstream effector caspases, such as caspase-3 and caspase-7, which execute the cell death program by cleaving various cellular substrates.

Regulation[edit]

The activity of the apoptosome is tightly regulated by several factors. IAPs can bind to and inhibit active caspases, thus preventing apoptosis. Additionally, the Bcl-2 family of proteins regulates the release of cytochrome c from the mitochondria, thereby controlling apoptosome formation. Pro-apoptotic members of the Bcl-2 family, such as Bax and Bak, promote cytochrome c release, while anti-apoptotic members, such as Bcl-2 and Bcl-xL, inhibit it.

Related pages[edit]