Related Experiment Video

Updated: Mar 25, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

8.4K

Small molecules reveal an alternative mechanism of Bax activation

Hetal Brahmbhatt1, David Uehling2, Rima Al-Awar2

  • 1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada, L8S 4L8 Department of Biological Sciences, Sunnybrook Research Institute, University of Toronto, ON, Canada, M4N 3M5.

The Biochemical Journal
|February 27, 2016
PubMed

Insights

Researchers discovered new small molecules that activate the pro-apoptotic protein Bax, independent of known pathways. These compounds trigger Bax oligomerization and cell death, offering novel insights into apoptosis regulation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • The pro-apoptotic protein Bax initiates programmed cell death by permeabilizing the mitochondrial outer membrane (MOM).
  • Understanding Bax activation mechanisms is crucial for controlling cell death pathways.

Purpose of the Study:

  • To identify small-molecule probes that elucidate Bax activation mechanisms.
  • To discover novel pathways for Bax activation.

Main Methods:

  • Screening for compounds inducing Bax-mediated liposome permeabilization.
  • Assessing compound effects on Bax targeting, oligomerization, and membrane interaction.
  • Evaluating compound-induced apoptosis in cells.
  • Investigating the role of specific Bax residues and inhibition by Bcl-XL.

Main Results:

  • Five structurally distinct small molecules were identified that promote Bax targeting and oligomerization at membranes.
  • These compounds initiated Bax oligomerization independently of membranes and BH3 proteins.
  • Some compounds induced Bax/Bak-dependent apoptosis in cells.
  • The most active compound's Bax activation was poorly inhibited by Bcl-XL and required Cys126, unlike BH3-mediated activation.

Conclusions:

  • A novel pathway for Bax activation, independent of pro-apoptotic BH3 proteins, has been revealed.
  • These findings suggest new strategies for regulating Bax activity and cell death.
  • The identified small molecules serve as valuable probes for studying Bax function.
Keywords:
Bax activatorsBax oligomerizationapoptosiscysteinemechanism probesmembrane permeabilization

More Related Videos

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

9.5K
Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

17.9K

Related Concept Videos

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...
9.1K
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...
9.2K
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
14.5K
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...
16.8K
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...
5.0K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
19.2K