Related Experiment Video

Updated: Jul 7, 2026

Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay
05:52

Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay

Published on: May 12, 2023

TNFalpha and reactive oxygen species in necrotic cell death

Michael J Morgan1, You-Sun Kim, Zheng-gang Liu

  • 1Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Cell Research
|February 28, 2008
PubMed

Insights

Death receptors trigger caspase-independent cell death via reactive oxygen species (ROS) production, with RIP1 as a central mediator. This necrotic cell death pathway may clear virus-infected cells.

Area of Science:

  • Cellular biology
  • Immunology
  • Biochemistry

Background:

  • Death receptors, such as TNF receptor-1 (TNF-RI), can initiate cell death pathways.
  • Caspase-independent cell death, termed necrotic cell death, is linked to reactive oxygen species (ROS) generation.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying TNF-RI-mediated necrotic cell death.
  • To identify key signaling molecules involved in ROS production and cell death.

Main Methods:

  • Investigated the role of NADPH oxidases in superoxide generation.
  • Examined the involvement of adaptor molecules RIP1 and TRADD in the death receptor complex.
  • Assessed the contribution of sustained JNK activation to necrotic cell death.

Main Results:

  • Superoxide generation is dependent on NADPH oxidase activation, forming a complex with RIP1 and TRADD.
  • RIP1 is identified as a central molecule in ROS production and TNFalpha-initiated cell death.
  • Sustained JNK activation is implicated in necrotic cell death.

Conclusions:

  • TNF-RI can initiate caspase-independent necrotic cell death dependent on ROS.
  • RIP1 plays a crucial role in mediating ROS production and cell death downstream of TNFalpha.
  • Necrotic cell death may serve as a mechanism for clearing virus-infected cells.

More Related Videos

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation06:12

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Published on: May 3, 2024

Related Concept Videos

Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
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...
Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cellular Injury IlI: Cellular Death01:11

Cellular Injury IlI: Cellular Death

Cell death is the irreversible loss of cellular structure and function, representing the final stage of severe injury. It plays a key role in both normal physiology and disease.Types of Cell DeathThe two main types are necrosis and apoptosis, though others like necroptosis and pyroptosis also exist.Necrosis:Necrosis is an unregulated form of cell death caused by severe injury such as trauma, toxins, or ischemia. It is characterized by cell swelling, membrane loss, rupture, and leakage of...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Cellular Injury I: Introduction01:00

Cellular Injury I: Introduction

Cellular injury occurs when a cell cannot maintain homeostasis or adapt to stressors such as hypoxia, toxins, or trauma. Depending on severity and duration, injury may be reversible, allowing recovery, or irreversible, leading to cell death.General Mechanisms of Cell InjuryAlthough causes vary, most cellular injuries arise from a few key mechanisms that disrupt essential functions and often amplify one another. Cell survival depends on the extent and balance of these disturbances.ATP depletion...