There are two main types of cell death: necrosis, which is uncontrolled cell death associated with disease, and apoptosis, which is programmed cell death that is essential for normal health and development with 50-70 billion cells dying each day through apoptosis. Apoptosis is triggered through two main pathways: receptor mediated and mitochondria mediated intrinsic pathways. Both pathways activate caspases, cysteine-aspartic proteases that exist as inactive pro-enzymes but can activate other caspases in a cascade once activated. The intrinsic pathway involves the release of cytochrome c from mitochondria, forming an apoptosome complex that activates caspase 9, an initiator caspase. The Bcl-2 family of proteins regulates cytochrome c release from
There are two main types of cell death: necrosis, which is uncontrolled cell death associated with disease, and apoptosis, which is programmed cell death that is essential for normal health and development with 50-70 billion cells dying each day through apoptosis. Apoptosis is triggered through two main pathways: receptor mediated and mitochondria mediated intrinsic pathways. Both pathways activate caspases, cysteine-aspartic proteases that exist as inactive pro-enzymes but can activate other caspases in a cascade once activated. The intrinsic pathway involves the release of cytochrome c from mitochondria, forming an apoptosome complex that activates caspase 9, an initiator caspase. The Bcl-2 family of proteins regulates cytochrome c release from
There are two main types of cell death: necrosis, which is uncontrolled cell death associated with disease, and apoptosis, which is programmed cell death that is essential for normal health and development with 50-70 billion cells dying each day through apoptosis. Apoptosis is triggered through two main pathways: receptor mediated and mitochondria mediated intrinsic pathways. Both pathways activate caspases, cysteine-aspartic proteases that exist as inactive pro-enzymes but can activate other caspases in a cascade once activated. The intrinsic pathway involves the release of cytochrome c from mitochondria, forming an apoptosome complex that activates caspase 9, an initiator caspase. The Bcl-2 family of proteins regulates cytochrome c release from
1. Necrosis: (uncontrolled cell death). Associated with disease. 2. Apoptosis (programmed cell death or cell suicide). Apoptosis is an essential part of normal health and development. In an average adult between 50 and 70 billion cells die through apoptosis per day. In a year your entire body weight of cells will have died through apoptosis. Importance of apoptosis 1. Immune system – destroying self-reacting immune cells. 2. Immune system – destroying virus infected cells. 3. Homeostasis – as a counter-balance to cell division and removal of old or damaged cells. Cancer – radiotherapy and most chemotherapy drugs work by inducing apoptosis. Many cancer cells have defects in the apoptosis pathways that make them resistant to apoptosis. How is apoptosis triggered? Two main pathways for triggering apoptosis: 1. Receptor mediated (extrinsic pathway) 2. Mitochondria mediated (intrinsic pathway). The intrinsic pathway can be activated by a variety of cell stresses such as free radical damage, DNA damage, viral infection, or loss of survival signals. Both pathways induce apoptosis by activating a class of proteases in the cell called caspases. Caspases - cysteine-aspartic proteases. A family of 12 proteases that exist as inactive pro-enzymes in cells. Following activation by cleavage they can activate other caspases in a cascade. There are two types of apoptotic caspases: 1. Initiator caspases: activate other caspases. 2. Effector (executioner) caspases: break down cellular components such as the cytoskeleton and DNA. Activation of caspases is the point of no return in the process of apoptosis. Role of mitochondria in apoptosis: Cytochrome C is located in the inner mitochondrial membrane and is an essential component of the electron transport chain. In the intrinsic apoptosis pathway, pores form in the outer mitochondrial membrane allowing release of cytochrome C into the cytosol. Since cytochrome C is normally only found in the mitochondria, its release into the cytosol acts as a trigger for apoptosis. Cytochrome C binds to other cytosolic proteins to form a multi-protein complex called the apoptosome. The formation of the apoptosome requires cytochrome C, a protein called Apaf-1, pro-caspase 9 and ATP. There are 7 molecules of each protein in the complete apoptosome with a combined molecular weight of 700 KDa. The end result is the cleavage and therefore activation of pro-caspase 9 into active caspase 9, an initiator caspase.
What controls the release of cytochrome C from the mitochondria?
The Bcl-2 family of proteins is responsible for the regulation of cytochrome C release from the mitochondria. There are around 20 members of the family and consist of both pro-apoptotic and anti-apoptotic proteins. Their ability to induce apoptosis depends on the balance between the two types. The Bcl-2 family of proteins is responsible for the regulation of cytochrome C release from the mitochondria. There are around 20 members of the family and consist of both pro-apoptotic and anti-apoptotic proteins. Their ability to induce apoptosis depends on the balance between the two types. Anti-apoptotic members are thought to exist in the mitochondrial outer membrane and act to block the action of the pro-apoptotic members.