Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

8.1K
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...
8.1K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

7.9K
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...
7.9K
Autophagic Cell Death01:18

Autophagic Cell Death

4.3K
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...
4.3K
Apoptosis01:30

Apoptosis

13.8K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' 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...
13.8K
Overview of Cell Death01:30

Overview of Cell Death

9.2K
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...
9.2K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

4.9K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.9K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

The MIRO1-BAX Complex Dictates Life and Death at the Mitochondrial Gate.

bioRxiv : the preprint server for biology·2026
Same author

High-throughput measurements of protein domain functions using magnetic separation.

Nature protocols·2026
Same author

Cell size modulates ferroptosis susceptibility.

eLife·2026
Same author

An image-based CRISPR screen reveals splicing-mediated control of HP1α condensates.

bioRxiv : the preprint server for biology·2026
Same author

Programmable synthetic cytokine receptors polarize macrophages to user-defined functional states.

bioRxiv : the preprint server for biology·2026
Same author

Organoid modeling of tumor-associated macrophages reveals phagocytosis checkpoint blockade-induced conversion to an immunosuppressive SPP1+ phenotype.

bioRxiv : the preprint server for biology·2026

Related Experiment Video

Updated: Jan 5, 2026

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

2.9K

A ZDHHC5-GOLGA7 Protein Acyltransferase Complex Promotes Nonapoptotic Cell Death.

Pin-Joe Ko1, Claire Woodrow1, Michael M Dubreuil2

  • 1Department of Biology, Stanford University, Stanford, CA 94305, USA.

Cell Chemical Biology
|October 22, 2019
PubMed
Summary

A novel small molecule, caspase-independent lethal 56 (CIL56), triggers a unique non-apoptotic cell death pathway. This process involves the ZDHHC5-GOLGA7 protein complex and disrupts protein transport, offering new insights into cell death mechanisms.

Keywords:
GOLGA7Golgi apparatusPATZDHHC5necrosisnonapoptotic cell deathoximepalmitoylation

More Related Videos

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
13:21

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila

Published on: November 27, 2016

9.5K
Evaluation of Caspase Activation to Assess Innate Immune Cell Death
10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.7K

Related Experiment Videos

Last Updated: Jan 5, 2026

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

2.9K
In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
13:21

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila

Published on: November 27, 2016

9.5K
Evaluation of Caspase Activation to Assess Innate Immune Cell Death
10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.7K

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Pharmacology

Background:

  • Lethal small molecules are crucial tools for investigating cell death pathways.
  • Understanding novel cell death mechanisms beyond apoptosis is a key area of research.

Purpose of the Study:

  • To characterize the mechanism of cell death induced by the small molecule CIL56.
  • To identify the molecular players involved in CIL56-induced cell death.
  • To define a novel non-apoptotic cell death pathway.

Main Methods:

  • Treatment of cells with CIL56 and structurally related oxime-containing molecules.
  • Biochemical assays to identify protein interactions and enzymatic activity.
  • Cellular transport assays to assess protein trafficking.
  • Genetic manipulation to study the role of ZDHHC5 and GOLGA7.

Main Results:

  • CIL56 induces a form of nonapoptotic cell death distinct from necroptosis and ferroptosis.
  • CIL56-induced cell death requires a functional ZDHHC5-GOLGA7 protein S-acyltransferase complex.
  • The ZDHHC5-GOLGA7 complex localizes to the plasma membrane and is essential for cell survival.
  • CIL56 inhibits anterograde protein transport from the Golgi apparatus.

Conclusions:

  • CIL56 defines an unconventional non-apoptotic cell death pathway regulated by protein S-acylation.
  • The ZDHHC5-GOLGA7 complex plays a critical role in this novel cell death pathway.
  • Disruption of protein transport is a key lethal event in CIL56-induced cell death.