Cell Death

Cell death
By: Saima
Assistant professor
Magadh institute of pharmacy
• Cell death is essential for maintaining tissue homeostasis, eliminating
damaged cells, and responding to stress or injury.
• The two main types of cell death are
1. Apoptosis (programmed cell death)
2. Necrosis (uncontrolled or pathological cell death).
3. Autophagy, also plays a role in cell death under certain conditions.
Apoptosis
• Apoptosis is a highly regulated and controlled process by which cells
die without causing an inflammatory response.
• It is a normal physiological process in development, tissue
maintenance, and immune response.
• Apoptosis occur by two basic types of pathways:
1. extrinsic pathway ( Death receptor pathway)
2. Intrinsic pathway (Mitochondrial pathway)
Mechanism of apoptosis
Mitochondrial
Cellular Stress or Activation of Pro- Release of
Membrane
Damage apoptotic Proteins Cytochrome c
Permeabilization
Binding to Cytc
Cell Breakdown and Activation of
Activation of with Apaf-1 &
formation of Caspase-3,
Caspase-9 Formation of the
apoptotic bodies Caspase-7
Apoptosome
Apaf-1 (Apoptotic protease-activating factor-

Removal by 1).
Phagocytosis
• The intrinsic pathway of apoptosis is usually triggered by internal cell stress or damage such as
DNA damage (from radiation or toxins), oxidative stress (free radicals), or lack of survival signals
(growth factors).
• In response to the stress, certain proteins called pro-apoptotic proteins (like Bax and Bak) are
activated.
• Mitochondrial damage: Bax and Bak proteins move to the outer membrane of the mitochondria
(the powerhouse of the cell).
• They make the mitochondrial membrane permeable (leaky), allowing important proteins inside
the mitochondria to escape into the cytoplasm (the cell fluid).
• One of the most important proteins released from the mitochondria is cytochrome c.
• Building the apoptosome: Cytochrome c in the cytoplasm binds to a protein called Apaf-1
(apoptotic protease-activating factor-1).
• Caspase activation: The apoptosome then activates an enzyme called caspase-9.
• Caspase-9 role: This enzyme is part of a family of enzymes called caspases, which are responsible
for breaking down the cell in an orderly way.
• Caspase-9 activates other enzymes such as caspase-3 and caspase-7.
• These caspases go on to dismantle the cell by breaking down its proteins and DNA.
• Cell dismantling: As caspases break down the components of the cell, it begins to shrink and form
small membrane-bound pieces called apoptotic bodies.
• These apoptotic bodies are then engulfed by nearby immune cells (like macrophages) and safely
removed from the body, without causing inflammation or harm to surrounding tissues.
APOPTOSOME
Bak
NECROSIS
• Necrosis is a form of cell death resulting from irreversible injury to
cells, leading to the breakdown of cell structure and leakage of
cellular contents into the surrounding tissue.
• It differs from apoptosis (programmed cell death) in that it is typically
unregulated and often associated with inflammation.
• The mechanism of necrosis involves a series of pathological events
leading to uncontrolled cell death.
• Unlike apoptosis, necrosis is usually triggered by external factors like
trauma, infection, or ischemia (lack of blood flow), causing
irreversible cellular damage.
MECHANISM OF NECROSIS
1. Cellular Injury and Membrane
Damage
2. Mitochondrial Dysfunction
3. Increased Intracellular
Calcium
4. Enzyme Activation and Cell
Destruction
5. Membrane Rupture and
Leakage
6. Inflammation
1. Cellular Injury and Membrane Damage
• Necrosis starts with severe cellular injury that disrupts the integrity of the
cell membrane:
• Ischemia (lack of oxygen), toxins, or trauma can damage the plasma
membrane.
• The damaged membrane becomes permeable, allowing ions, water, and
harmful molecules to enter the cell.
• Cell swelling (oncosis) occurs as water and sodium accumulate inside due
to the failure of ion pumps, particularly the Na⁺/K⁺-ATPase pump.
2. Mitochondrial Dysfunction
• Injury to mitochondria causes a loss of ATP production, which is

vital for maintaining cellular functions.
• ATP depletion prevents energy-dependent processes, such as
maintaining ion gradients and repairing the cell membrane.
• Mitochondrial damage also leads to the release of reactive
oxygen species (ROS) and pro-apoptotic factors, which further
damage cellular structures.
3. Increased Intracellular Calcium
• Injury to the membrane allows excessive calcium ions (Ca²⁺) to enter the
cell.
• High intracellular calcium levels activate several harmful enzymes,
including:
• Proteases: Break down proteins.
• Phospholipases: Degrade phospholipids in the cell membrane.
• Endonucleases: Fragment DNA.
• ATPases: Deplete remaining ATP stores.
4. Enzyme Activation and Cell Destruction
• The activated enzymes destroy structural components of the cell:

• Proteins, lipids, and nucleic acids in the cell are degraded, leading
to the breakdown of essential cellular functions.
• The cytoskeleton (structural framework of the cell) collapses,
and cellular organelles, such as the nucleus, mitochondria, and
endoplasmic reticulum, are damaged.
5. Membrane Rupture and Leakage
• As damage progresses, the plasma membrane becomes

increasingly porous, leading to the rupture of the cell
membrane.
• Cellular contents, including lysosomal enzymes and other
harmful substances, leak out into the extracellular
environment.
• This leakage triggers an inflammatory response, as immune
cells like neutrophils and macrophages are recruited to the site
of necrosis to clear dead cells and tissue debris.
6. Inflammation
• The extracellular release of intracellular contents, such

as enzymes, proteins, and other cellular debris, is
recognized as damage by the immune system.
• Inflammation occurs as the immune system attempts to
remove dead tissue. This process often involves the
release of pro-inflammatory cytokines, leading to tissue
swelling, redness, and further damage to surrounding
cells.
APOPTOSIS VS NECROSIS
Aspect Apoptosis Necrosis
Programmed, regulated
Nature Uncontrolled, accidental cell death
cell death
DNA damage, oxidative stress, withdrawal of growth

Trauma, toxins, infections, ischemia, extreme
Causes/Triggers factors, mitochondrial dysfunction, immune signals
temperatures, radiation
(e.g., Fas, TNF)
Does not require energy (occurs due to energy

Energy Requirement Requires energy (ATP) for an active process
depletion)
- Cell shrinkage - Cell swelling

- Chromatin condensation - Membrane rupture
Cell Morphology
- Membrane blebbing - Cell lysis
- Apoptotic bodies formation - Nuclear dissolution
Process Controlled, systematic dismantling of the cell Chaotic, disorganized breakdown of the cell
Causes inflammation and damage to surrounding

Inflammation No inflammation (cleaned up by phagocytes)
tissues
Normal in development, immune system function,

Physiological Role Abnormal, associated with injury, infection, or disease
tissue homeostasis
Cell fragments are engulfed and digested by

Outcome Cell contents spill out, damaging surrounding tissue
neighboring cells (no spillage)
Casualties Typically a single cell or a few cells Often affects groups of cells and surrounding tissue
Embryonic development, immune regulation, cancer

Example Conditions Ischemic injury (heart attack, stroke), trauma, infection
therapy

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Cell death

Apaf-1 (Apoptotic protease-activating factor-

• Injury to mitochondria causes a loss of ATP production, which is

• The activated enzymes destroy structural components of the cell:

• As damage progresses, the plasma membrane becomes

• The extracellular release of intracellular contents, such

DNA damage, oxidative stress, withdrawal of growth

Does not require energy (occurs due to energy

- Cell shrinkage - Cell swelling

Causes inflammation and damage to surrounding

Normal in development, immune system function,

Cell fragments are engulfed and digested by

Embryonic development, immune regulation, cancer

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