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Overview of Cell Death

Overview of Cell Death

Mechanisms and Types of Cell Death

Cells can die in a number of different manners, depending on the cellular context and triggering stimulus.

Types of Cell Death

Cell death mechanisms include:

Apoptosis - programmed cell death that occurs during growth and development and can also occur in response to harmful environmental stimuli.
Necrosis - can be a passive or an active, regulated process such as necroptosis or pyroptosis.

Different assays can be used to determine the mechanism of cell death or rule out a mechanism of cell death within a cellular population.

Apoptosis

Apoptosis is a highly regulated form of programmed cell death that occurs in multicellular organisms during development, throughout the lifespan, and in response to cellular stress. Apoptosis is mediated by a family of proteolytic enzymes called caspases. Other proteins, including proapoptotic and antiapoptotic proteins, also play important roles.

Dysregulation of apoptosis occurs in several disease states, including autoimmune disorders, neurodegenerative diseases, and cancer.

Apoptosis is a form of programmed cell death mediated by caspases and a host of other proteins.

Regulation of Apoptosis: Interactive Pathway >>

How to Measure Apoptosis

Apoptotic cells can be distinguished from viable cells by phenotypic changes and activity of certain proteins. Several different methods can be used to analyze and measure levels of apoptosis within a population. These assays include:

Assay

Annexin V assay

What is Measured

Detects changes that occur to the lipid bilayer early in apoptosis

Assay

TUNEL Kits
DNA fragmentation which is a hallmark of apoptosis

What is Measured

Assay

Caspase cleavage

What is Measured

Cleavage of caspase-3, caspase activity assay, and cleavage of other caspases and PARP are frequently used readouts for apoptosis

Assay

Chromatin condensation

What is Measured

Detects apoptotic cells with condensed chromatin after staining with nuclear dyes, such as DAPI or Hoechst 33342

Assay

Cytochrome c release

What is Measured

Translocation of cytochrome c from mitochondria to the cytoplasm is a hallmark feature of apoptotic cells

Assay

Mitochondrial membrane potential assay

What is Measured

Depolarization and subsequent decrease of the mitochondrial membrane potential is a hallmark feature of apoptotic cells

Necrosis

Necrosis has been classically defined as an unprogrammed cell death that occurs following acute injury or infection or when apoptosis is inhibited and is characterized by cellular swelling and lysis. Necrotic cells release intracellular contents into the surrounding environment, which activates an inflammatory response to recruit phagocytes to clear dead cells. Uncontrolled, however, necrosis can cause severe tissue damage, such as gangrene.

Necrotic Cell Death Signaling Interactive Pathway >>

While it was previously thought that necrosis was passive and unprogrammed, recent data have uncovered different types of regulated necroptotic pathways.

Types of Regulated Necrosis

In addition to necrosis, other lytic cell death mechanisms include:

Necroptosis - a programmed and regulated form of necrosis which requires RIP3 and MLKL and is activated by pro-inflammatory signaling as well as ischemic injury and viral infection.
Pyroptosis - a form of programmed lytic cell death that typically occurs in immune cells in response to microbial or viral infection and requires caspase-1 and gasdermin-D