Biology Chapter on Apoptosis and Development

Programmed Cell Death (Apoptosis)

• Apoptosis is a controlled process of cellular suicide
• Occurs as a normal part of an organism's growth and development
• The body uses apoptosis to get rid of unneeded or abnormal cells
• The term apoptosis is derived from the Greek word describing the falling of leaves
• It is distinguished from accidental cell death caused by injury or inflammation

Animal Development

• Animal development starts with rapid proliferation of embryonic cells.
• These cells then differentiate into specialized cell types.
• This process creates the various tissues and organs of the adult organism.
• Humans have approximately 10¹⁴ cells with more than 200 differentiated cell types.
• Development begins with a single fertilized egg.

Cell Death and Proliferation

• Cell death and proliferation are balanced throughout the life of multicellular organisms.
• The balance is important for development and maintaining tissue health.

Types of Cell Death

• Apoptosis: A normal, controlled process where cells die by programmed cell death.
• Necrosis: Cell death resulting from injury, characterized by swelling, lysis, and inflammation.

Apoptosis Characteristics

• Neighboring cells remain healthy during apoptosis
• Apoptotic cell death doesn't typically lead to an inflammatory response
• Apoptotic bodies (cell fragments) are efficiently phagocytosed (engulfed) by neighboring cells and macrophages.
• It is an active process involving a series of cellular changes that lead to the death of the cell.

Apoptosis and Illnesses

• Abnormalities in apoptosis are linked to various illnesses, including cancer, autoimmune diseases, and neurodegenerative disorders (Parkinson's and Alzheimer's disease).

Cell Renewal

• In adult tissues, cell death must be balanced by cell renewal.
• Stem cells in tissues are capable of replacing lost cells.
• The ability of stem cells to differentiate into diverse cell types is crucial for tissue repair and maintenance.
• Embryonic stem cells are of great interest for therapeutic use in damaged tissues.

Apoptosis Pathway

• Two pathways are involved in apoptosis: Intrinsic and Extrinsic.

Intrinsic Pathway

• Activated by internal surveillance mechanisms signals (or not sent) from other cell
• Includes DNA damage, chemical exposure, interference with cellular pathways, and excessive cell-cycle activation.

Extrinsic Pathway

• Triggered by signals from other cells (external input),
• Killer cells directly interact with target cells.
• Target cell receptors activate specific pathways starting at the plasma membrane.

Apoptosis and the Immune System

• In the immune system, apoptosis is crucial for controlling cell populations.
• Cytotoxic T lymphocytes use apoptosis to eliminate infected cells.
• This prevents viral replication and spread.

Apoptosis and Cancer

• DNA damage can induce apoptosis, eliminating cells with potentially harmful mutations and preventing cancer development.

The Bcl-2 Family

• Proteins in this family are crucial regulators of apoptosis.
• This family has anti-apoptotic and pro-apoptotic members.
• These proteins interact to control cell death.

Apoptosis in Healthy Cells

• BAK is associated with the mitochondrial outer membrane (in healthy cells).
• BAX is located in the cytoplasm (in healthy cells).

Mechanisms of apoptosis

• Cytochrome C plays a key role in apoptosis.
• In the intrinsic pathway, cytochrome C is released from mitochondria, activates caspase proteins which lead to cell death.
• In the extrinsic pathway, Fas ligand activates caspase 8 to induce apoptosis.

Apaf-1

• Apaf-1 is a crucial protein in the intrinsic apoptosis pathway.
• Its conformational change allows for apoptosome formation.
• Binding to caspase 9 triggers activation and initiates the caspase cascade.

In the Cytoplasm

• Cytochrome C binds to Apaf-1 (apoptotic protease-activating factor-1), altering its conformation.
• This exposure allows Apaf-1 to form the apoptosome structure.

Apoptosis and Cell Death

• Apoptosis eliminates a cell neatly without causing inflammation, eliminating the defective cell.
• Cells that die due to injury swell and rupture and cause cell death.

Intrinsic Pathway

• Signal molecules (Bax, Bak) start the process by acting on the mitochondria.
• Cytochrome c release and caspase activation lead to Programmed Cell Death.
• Anti-apoptotic molecules (Bcl-2, Bcl-xL) inhibit mitochondria and prevent caspase activation thus preventing apoptosis.
• Binding of anti-apoptotic molecules to Bax/Bak prevents mitochondrial outer membrane permeabilization.

BH3-Only Family Proteins

• BH3-only proteins can directly or indirectly promote death by facilitating Bax/Bak oligomerization or binding/neutralizing anti-apoptotic Bcl-2 proteins.

Additional Factors

• Withdrawal of nutrients or survival signals from the environment can trigger apoptosis.
• Growth factors.
• Contact with neighboring cells
• The extracellular matrix are all important factors for cell survival or triggering cell death.

Common Causes of Programmed Cell Death

• Defective cells
• Cells overproduced
• Cells without function
• Cells with abnormal cell cycle
• Virus-infected cells
• Treatment with chemotherapy