Related Experiment Video

Updated: Jun 20, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Nitric oxide induces cell death by regulating anti-apoptotic BCL-2 family members

Colleen M Snyder1, Emelyn H Shroff, Jing Liu

  • 1Department of Medicine, Northwestern University Medical School, Chicago, Illinois, United States of America.

Plos One
|September 22, 2009
PubMed

Insights

Nitric oxide (NO) triggers apoptosis by degrading MCL-1 via the ASK1-JNK1 pathway, leading to BAX/BAK activation and cell death. This mechanism is independent of reactive oxygen species.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Nitric oxide (NO) is known to induce cell death through the intrinsic apoptotic pathway.
  • The precise molecular mechanisms by which NO activates this pathway remain largely unknown.
  • Understanding NO-induced apoptosis is crucial for various physiological and pathological processes.

Purpose of the Study:

  • To elucidate the mechanism of nitric oxide (NO)-induced apoptosis.
  • To identify the key proteins and pathways involved in NO-mediated cell death.
  • To investigate the role of BAX, BAK, and BH3-only proteins in NO-induced apoptosis.

Main Methods:

  • Utilized knockout/knockdown cell models (Bax/Bak deficient, Caspase-9 deficient, Ask1/Jnk1 deficient, and BH3-only protein deficient cells).
  • Investigated the activation of BAX and BAK, and release of cytochrome c.
  • Assessed the degradation of MCL-1 and the involvement of the ASK1-JNK1 signaling axis.
  • Evaluated the role of reactive oxygen species (ROS) and peroxynitrite.

Main Results:

  • NO activates BAX and BAK, leading to mitochondrial cytochrome c release and apoptosis.
  • Cells lacking Bax/Bak or Caspase-9 are protected from NO-induced cell death.
  • BH3-only proteins are not essential for NO-induced apoptosis.
  • NO induces degradation of the anti-apoptotic protein MCL-1 through the ASK1-JNK1 pathway.
  • MCL-1 degradation and subsequent apoptosis are dependent on ASK1 and JNK1.
  • ROS and peroxynitrite scavengers do not prevent NO-induced cell death, indicating a non-ROS dependent mechanism.

Conclusions:

  • Nitric oxide (NO) induces apoptosis by degrading MCL-1 via the ASK1-JNK1 signaling cascade.
  • This degradation leads to the activation of BAX and BAK, culminating in cell death.
  • The findings reveal a novel pathway for NO-induced apoptosis, independent of ROS and peroxynitrite.

More Related Videos

Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay05:52

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

Published on: May 12, 2023

Related Concept Videos

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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...