Necrosis & Apoptosis

Necrosis

• Accidental cell death

• Is the premature and uncontrolled death of cells due to factors like infection, toxins, trauma, or lack of blood supply

Cellular Swelling

Cells often swell due to water influx, leading to rupture of cell membranes

Loss of membrane integrity

Cellular contents leak out, causing inflammation in surrounding tissues

Inflammation

Necrosis triggers an immune response, leading to inflammation in the affected area

Coagulative Necrosis

Most common type of necrosis, often seen in ischemic conditions; tissue architecture is preserved intially

Liquefactive Necrosis

Occurs in tissues with high enzyme activity, such as in brain infarcts or abscessses; tissue turns to liquid

Caseous Necrosis

A combination of coagulative and liquefactive necrosis, seen in tuberculosis; tissue has a cheese-like appearance

Fat Necrosis

Occurs in fatty tissues

Gangrenous Necrosis

A subtype of coagulative necrosis involving large areas of tissue, often in limbs due to poor circulation

Apoptosis

• Programmed cell death

• Is a controlled, energy-dependent process of programmed cell death

Intrinsic Pathway

• Mechanisms of apoptosis

• Triggered by internal signals such as DNA damage or mitochondrial dysfunction. Involves activation of proteins called caspases, which break down cellular components

Extrinsic Pathway

• Mechanisms of apoptosis

• Triggered by external signals such as binding of death ligands to cell surface receptors. This activates caspses to carry out the apoptotic process

Bcl-2 Family

Proteins that are activated, in response to internal signals such as DNA damage or oxidative stress. Leading to mitochondrial outer membrane permeabilization (MOMP)

Cytochrome C

A key protein found in the intermembrane space of mitochondria.

Apaf-1

Cytochrome C enters the cytoplasm, where it binds to a specfic protein called?, forming a complex known as the apoptosome

Executioner Caspases

Once caspase-9 is activated, it intiates, which cleave various proteins in the cell, leading to the systematic breakdown of cellular components

p53

The tumor suppressor protein, plays a crucial role in the intrinsic pathway. When DNA is damaged, it activates and can promote the transcription of pro-apoptotic proteins like Bax and Puma, pushing the cell towards apoptosis

Fas Ligand (FasL)

A death ligands, that bind to specific death receptors on the cell surface

CD95 and TNFR1

A common death receptors. These receptors have an intracellular death domain that is crucial for signaling apoptosis

Fas-associated Death Domain (FADD)

Upon ligand binding, the intracellular part of the receptor recruits an adaptor protein called?

Pro-caspase-8

An inactive precursor of caspase-8, is also recruited to the receptor complex, forming the death-inducing signaling complex