Related Experiment Video

Updated: Dec 3, 2025

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
06:12

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum

Published on: May 3, 2024

2.9K

Pore formation in regulated cell death

Hector Flores-Romero1, Uris Ros1, Ana J Garcia-Saez1

  • 1Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

The EMBO Journal
|October 30, 2020
PubMed

Insights

Different proteins like BAX/BAK, Gasdermins, and MLKL cause cell death by permeabilizing membranes. This study compares their distinct mechanisms, revealing common principles in regulated cell death execution.

Area of Science:

  • Cell Biology
  • Biophysics

Background:

  • Regulated cell death pathways, including apoptosis, pyroptosis, and necroptosis, have diverse molecular components but share membrane permeabilization as a common execution step.
  • While BAX/BAK, Gasdermins, and MLKL oligomerize and form pores, they act on different cellular membranes through distinct mechanisms.

Purpose of the Study:

  • To compare and contrast the mechanisms by which BAX/BAK, Gasdermins, and MLKL induce membrane permeabilization.
  • To discuss the general principles governing membrane perforation in regulated cell death.

Main Methods:

  • Structural and biophysical analysis of pore-forming proteins involved in cell death.
  • Comparative review of BAX/BAK, Gasdermins, and MLKL functions.

Main Results:

  • BAX/BAK permeabilize the outer mitochondrial membrane, Gasdermins perforate the plasma membrane in pyroptosis, and MLKL does so in necroptosis.
  • These effectors, despite sharing oligomerization, utilize distinct structural and biophysical strategies to alter membrane permeability.

Conclusions:

  • Membrane permeabilization is a conserved execution mechanism across diverse regulated cell death pathways.
  • Understanding the specific mechanisms of BAX/BAK, Gasdermins, and MLKL provides insights into the fundamental principles of cell death regulation.
Keywords:
apoptosiscell deathmembrane poresnecroptosispyroptosis

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

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

Published on: December 27, 2016

9.0K
Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.6K

Related Concept Videos

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...
8.7K
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...
5.7K
Apoptosis01:30

Apoptosis

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...
13.2K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
37.7K
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...
7.4K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.8K