Cytosolic cytochrome C plays an important function in
Correct Answer: Apoptosis
Description: Ans. is 'a' i.e. Apoptosis Apoptosis is a programmed cell death.Mechanism of ApoptosisApoptosis is induced by a cascade of molecular events that may be initiated in distinct ways but culminate in the activation of caspases.Caspases are central to the pathogenesis of apoptosisThe process of apoptosis is divided into two phasesInitiation phase - During this phase caspases become catalytically activeExecution phase - During this phase caspases act to cause cell death.Initiation phase of apoptosisInitiation of apoptosis occurs principally by signals from two distinct but convergent pathwaysExtrinsic or receptor-initiated pathwayIntrinsic or mitochondrial pathwayExtrinsic or death receptor-initiated pathwayThis pathway is initiated by expression of cell surface death receptors on a variety of cells.Death receptors are members of tumor necrosis factor receptor family that contain a cytoplasmic domain involved in protein-protein interactions that are called death domain because it is essential for delivering apoptotic signals (or death signals)The best-known death receptors are the type 1 TNF receptor (TNFRI) and a related protein called Fas (CD95).When the Fas receptors are cross-linked by its ligand it triggers a sequence of events which eventually leads to activation of caspases.This pathway of apoptosis can be inhibited by a protein called FLIP, which can bind to inactive or procaspases but cannot cleave and activate these enzymes.The intrinsic mitochondrial pathwayThis pathway has no role for death receptors.This pathway is the result of increased mitochondrial permeability and the release of proapoptotic molecules in the cytoplasm.Note that antiapoptotic proteins reside in the mitochondrial membrane (Bcl-2 and Bcl-X).When cells are deprived of survival signals or subjected to stress Bcl-2 and Bcl-X are lost from the mitochondrial membrane and are replaced by proapoptotic members of the family such as Bak, Bax, and Bim.This leads to increase in the permeability of the mitochondrial membrane.Due to increased permeability of the mitochondrial membrane, several proteins that can activate the caspase leak out.One of these proteins is cytochrome C, well known for its role in mitochondrial respiration.In the cytoplasm, cytochrome binds to a protein called Apaf-1 (apoptosis-activating factor-1) and the complex activates caspase.* So, the final result of both the pathways that are extrinsic receptor mediated pathway and the intrinsic mitochondrial pathway is the same i.e. activation of the caspase.The execution phase of apoptosisAfter being activated the caspases act on many cellular components.They cleave cytoskeletal and nuclear matrix proteins and thus disrupts the cytoskeleton.They also lead to the breakdown of the nucleus.In the nucleus, the' target of caspase activation includes proteins involved in transcription, DNA replication andDNA repair.
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