Name: apoptosis and cell survival control
Uploaded: 2023-04-30T10:27:56.000Z
Duration: 1 min 30 s
Channel: JoVE

Apoptosis is a programmed cell death process where specific signals lead to the death of unwanted or potentially harmful cells.
The intrinsic or mitochondrial-mediated apoptotic pathway is triggered by intracellular death signals produced due to DNA damage, hypoxia, and biochemical stress such as oxidative stress. In contrast, the extrinsic apoptotic pathway is initiated when extracellular death-inducing ligands, such as cytokines, bind to the death receptors present on the cell surface.
The key mediators of apoptosis are proteases called caspases. Initiator caspases are activated by both intrinsic and extrinsic apoptotic pathways through different mechanisms.
Each initiator caspase then activates multiple executioner caspases.
In both pathways, the activated executioner caspases cleave cellular proteins causing morphological changes, such as cell shrinkage, nuclear fragmentation, and plasma membrane blebbing.
Next, the cellular components are enclosed into membrane vesicles called apoptotic bodies, which are then engulfed by phagocytic cells.
Through these steps, apoptosis results in controlled and contained cell death without causing inflammation and damage to the neighboring cells.

apoptosis

Apoptosis

Apoptosis is a combination of two Greek words, &#39;apo&#39;&#160;and &#39;ptosis,&#39;&#160;meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue. After examining the tissue under an electron microscope, he observed that the hepatocytes had shrunk and the chromatin had condensed. In 1980, Wyllie established the relationship between DNA degradation and apoptosis.
Apoptosis allows a cell to die in a controlled manner that prevents the release of potentially damaging molecules from inside the cell to the extracellular space. Many internal checkpoints monitor a cell&#39;s health. If abnormalities are observed, a cell can spontaneously initiate apoptosis. However, the cell&#39;s standard checks and balances fail in some cases, such as during viral infection or uncontrolled cell division due to cancer. External signaling can also initiate apoptosis. For example, most normal animal cells have receptors that interact with the extracellular matrix, a network of glycoproteins that provides structural support for cells in an organism. The binding of cellular receptors to the extracellular matrix initiates a signaling cascade within the cell. However, if the cell moves away from the extracellular matrix, the signaling ceases, and the cell undergoes apoptosis. This system prevents cells from traveling through the body and proliferating out of control, as happens with tumor cells that metastasize.
Regulated apoptosis is essential to maintain normal physiology and tissue homeostasis. Dysregulated apoptosis in cells leads to various diseases, such as cancer, Alzheimer&#39;s, and cardiovascular diseases. Dysregulated apoptosis can also cause increased apoptosis, as observed during various autoimmune diseases like Hashimoto&#39;s thyroiditis, systemic lupus erythematosus, and rheumatoid arthritis.
Some portion of this text is adapted from <a href="https://openstax.org/books/biology-2e/pages/9-3-response-to-the-signal">Openstax, Biology 2e, Section: 9.3</a>

Apoptosis is a combination of two Greek words, &#39;apo&#39;&#160;and &#39;ptosis,&#39;&#160;meaning separation and falling off, respectively. Hippocrates ...

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JoVE Core

Cell Biology

Unit 1

Cell Death

KEY TERMS AND CONCEPTS

apoptosis and cell survival control

Apoptosis is a controlled form of cell death that helps keep tissues healthy. The term comes from two Greek words, apo and ptosis, which mean separation and falling off. Hippocrates used the word to describe gangrene caused by bandaging fractured bones.

Apoptosis was separated from necrosis in 1970 after John Kerr described its distinct shape changes. In one experiment, loss of blood supply to liver tissue caused the tissue to shrink. Under an electron microscope, Kerr saw that hepatocytes had shrunk and the chromatin had condensed. In 1980, Wyllie linked DNA degradation to apoptosis.

This process lets a cell die in a controlled way. That control helps prevent damaging molecules inside the cell from spilling into the extracellular space, or the area outside the cell. Cells also use internal checkpoints to monitor health. If problems are detected, a cell can trigger apoptosis on its own.

Apoptosis can also begin through external signals. Most normal animal cells have receptors that bind to the extracellular matrix, a network of glycoproteins that supports cells in the body. When these receptors attach, a signaling cascade starts inside the cell. If the cell moves away from the extracellular matrix, the signal stops and apoptosis begins. This helps stop cells from spreading through the body and dividing out of control, as occurs with tumor cells that metastasize.

When apoptosis is properly regulated, it supports normal physiology and tissue homeostasis, which means keeping body conditions stable. When it is dysregulated, disease can result. Too little apoptosis is linked with cancer, Alzheimer’s disease, and cardiovascular diseases. Too much apoptosis can also be harmful, as seen in autoimmune diseases such as Hashimoto’s thyroiditis, systemic lupus erythematosus, and rheumatoid arthritis.

Apoptosis and Cell Survival Control

overview of cell death

Cell Death Pathways in Cells

Cell death pathways help the body remove old or damaged cells. Cell growth and cell death must stay balanced. If this balance is disrupted, it may contribute to cancer or autoimmune diseases. Cell death was first noticed in the early 19th century, but experimental proof came later. In 1842, Carl Vogt described cell death in a metamorphic toad. At that time, the process was not yet called cell death. Scientists identified separate cell death pathways in the 20th century after advances in...

Apoptosis is a controlled form of cell death that helps keep tissues healthy. The term comes from two Greek words, apo and ptosis, which mean separation and falling off. Hippocrates used the word to describe gangrene caused by bandaging fractured bones. Apoptosis was separated from necrosis in 1970 after John Kerr described its distinct shape changes. In one experiment, loss of blood supply to liver tissue caused the tissue to shrink. Under an electron microscope, Kerr saw that hepatocytes had...

caspases

Caspases in Apoptosis and Immunity

Caspases are cysteine proteases that help control cell death and immune defense. They act as effectors in apoptosis, which is the process of programmed cell death. The ced-3 gene in C. elegans was first linked to apoptosis, and it encodes a caspase similar to the interleukin-1-beta converting enzyme, or ICE, in mammals. Caspases also have a role in inflammation. Inflammatory caspases activate pro-inflammatory cytokines, which help recruit immune cells and stop pathogens from replicating inside...

the extrinsic apoptotic pathway

How Immune Cells Trigger Cell Death

The extrinsic apoptotic pathway is a cell death process started by signals from outside the cell. In this pathway, extracellular death signals such as specific cytokines activate death receptors on the cell surface. Natural killer cells, or NK cells, and cytotoxic T-lymphocytes help carry out this response. NK cells are part of the innate immune response, while cytotoxic T-lymphocytes belong to the adaptive immune response. These cells recognize receptors on altered cells and activate...

the intrinsic apoptotic pathway

How Cells Trigger Apoptosis from Damage

Intrinsic apoptosis is the cell’s built-in death response to internal stress. Cell injury, hypoxia, and DNA damage can start this process. The B-cell lymphoma 2, or Bcl-2, family of proteins is the main regulator of this pathway. When DNA is damaged, checkpoint proteins such as Ataxia Telangiectasia Mutated, or ATM, and Checkpoints Factor-2, or Chk2, become active. They phosphorylate p53, a protein that helps control cell survival. p53 then turns on pro-apoptotic proteins such as Bax, Bak,...

phagocytosis of apoptotic cells

How Apoptotic Cells Are Cleared

Apoptotic cells must be cleared quickly so they do not cause inflammation, autoimmune disease, or necrosis. During apoptosis, cells break into apoptotic bodies that are then removed by phagocytosis, the process in which other cells engulf and digest them. Professional phagocytes, such as macrophages and immature dendritic cells, handle this job most effectively. Some non-professional phagocytes, including epithelial cells and fibroblasts, can also take part, but they are less efficient. Normal...

autophagic cell death

Autophagy and Cell Death Pathways

Autophagy is a cell cleanup process that can also lead to cell death. Christian de Duve discovered autophagy, in which cell parts are enclosed in membrane-bound sacs called autophagosomes. These autophagosomes then fuse with lysosomes, which digest the material inside. In many cells, autophagy helps prevent cell death. When damage becomes too severe to repair, however, the process can shift toward cell death. Autophagy can connect to apoptosis, necroptosis, and autosis, so it sits at an...

necrosis

Necrosis and Other Cell Death Pathways

Necrosis is an accidental form of cell death that ends in cell lysis, or cell bursting. Rudolf Virchow first used the term in 1859 in his book Cell Pathology to describe advanced tissue breakdown. In high school biology, necrosis is often used to compare damaged cells with other ways cells can die. Necrotic cells can look different depending on the tissue and the cause of injury. In coagulative necrosis, cells lose their nuclei but keep their basic shape because the enzymes that digest cell...

key terms and concepts

Learn how apoptosis controls cell survival, how it differs from necrosis, and why problems in this process are linked to cancer and autoimmune disease.

Apoptosis and Cell Survival Control | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

Apoptosis and Cell Survival Control

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