Name: necrosis and other cell death pathways
Uploaded: 2023-04-30T10:28:41.000Z
Duration: 1 min 16 s
Channel: JoVE

Necrosis is a type of cell death where the cell membrane ruptures, and the released cellular components cause local inflammation.
Necrosis occurs in both a non-programmed and a programmed manner.
Non-programmed necrosis is a passive process that does not involve a specific intracellular signaling pathway. It is triggered when a cell is damaged by severe stress, such as physical injury.
The accompanying mitochondrial damage causes a decrease in ATP production. There is also an increase in intracellular calcium concentration, which leads to cell swelling and bursting.
Programmed necrosis or necroptosis is a backup pathway for apoptosis that occurs when procaspases are not correctly activated. Necroptosis is regulated by the kinases RIP1 and RIP3 that form complexes with apoptotic signaling pathway components.
RIP3 phosphorylates the pore-forming protein MLKL, causing it to oligomerize and form a pore in the membrane. This opening allows a calcium and sodium ion influx, resulting in membrane rupture and cell death.

necrosis

Necrosis

Necrosis is considered as an &#8220;accidental&#8221; or unexpected form of cell death that ends in cell lysis. The first noticeable mention of &#8220;necrosis&#8221; was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled &#8220;Cell Pathology&#8221;.
<h4>Morphological Manifestations of Necrosis</h4>
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their architecture remains intact, due to damage to the proteolytic enzymes responsible for cell digestion. Fibrinoid necrosis occurs in blood vessels when the endothelium is damaged, and fibrin is deposited on the vessel wall. Fat necrosis occurs when damage to adipose tissue releases the lipids stored in these cells. For example, during acute pancreatitis, the pancreatic enzymes digest the surrounding fat cells. These fatty acids that are released combine with calcium and produce chalky white soap deposits. Liquefactive necrosis is typically seen in the nervous system, where the necrotic tissue is digested into a viscous liquid. It can be present not only during an infection but also under hypoxic conditions, such as a nerve infraction.
<h4>Alternate Pathways of Cell Death</h4>
In addition to apoptosis and necrosis, cells also exhibit death by necroptosis. Necroptosis has characteristics of both necrosis and apoptosis. It follows a specific signaling pathway like apoptosis, but similar to necrosis, it results in membrane rupture and cell death. Necroptosis occurs during neurodegeneration, ischemia, and infection. Other forms of cell death include mitochondrial permeability transition (MPT) driven necrosis, parthanatos, and ferroptosis. During MPT-driven necrosis, an overload of Ca2+ and oxidative stress increases cyclophilin D production. This, in turn, increases mitochondrial permeability, resulting in mitochondrial rupture. The parthanatos pathway is initiated by the poly(ADP-ribose) polymerase 1 or PARP1 in response to excessive DNA damage due to factors such as oxidative stress. The long poly(ADP-ribose) polymers then bind apoptosis-inducing factors (AIF) that bring about cell death by increasing mitochondrial membrane permeability and chromatin fragmentation. In addition to DNA damage, oxidative stress can also lead to an accumulation of lipid peroxides resulting in cell death. This process is dependent on the availability of iron and is thus termed ferroptosis.

Necrosis is considered as an &#8220;accidental&#8221; or unexpected form of cell death that ends in cell lysis. The first noticeable mention of ...

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JoVE Core

Cell Biology

Unit 1

Cell Death

KEY TERMS AND CONCEPTS

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 material are damaged. Fibrinoid necrosis happens in blood vessels when the endothelium is injured and fibrin is deposited on the vessel wall.

Fat necrosis affects adipose tissue, or body fat, when the stored lipids are released from damaged cells. During acute pancreatitis, pancreatic enzymes digest nearby fat cells. The released fatty acids combine with calcium and form chalky white soap deposits. Liquefactive necrosis is common in nervous tissue, where the dead tissue is broken down into a thick liquid. It can occur during infection or under hypoxic conditions, such as a nerve infarction.

Cells can also die through other pathways besides apoptosis and necrosis. Necroptosis is a programmed pathway that shares features of both apoptosis and necrosis. It follows a signaling route like apoptosis, but it still causes membrane rupture and cell death like necrosis. Necroptosis can occur during neurodegeneration, ischemia, and infection.

Other cell death pathways include mitochondrial permeability transition, or MPT-driven necrosis, parthanatos, and ferroptosis. In MPT-driven necrosis, too much Ca2+ and oxidative stress increase cyclophilin D, which raises mitochondrial permeability and leads to mitochondrial rupture. Parthanatos begins when PARP1 responds to severe DNA damage, such as damage caused by oxidative stress, and the resulting poly(ADP-ribose) polymers bind AIF to increase mitochondrial membrane permeability and cause chromatin fragmentation. Ferroptosis also involves oxidative stress, but it depends on iron and the buildup of lipid peroxides.

Necrosis and Other Cell Death Pathways

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

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...

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 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

Explore necrosis, its major tissue patterns, and related cell death pathways including necroptosis, parthanatos, MPT-driven necrosis, and ferroptosis.

Necrosis and Other Cell Death Pathways | 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.

Necrosis and Other Cell Death Pathways

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