Related Experiment Video

Updated: Jun 21, 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

Requirement of voltage-dependent anion channel 2 for pro-apoptotic activity of Bax

H Yamagata1, S Shimizu, Y Nishida

  • 1Department of Medical Genetics, Osaka University Medical School, Suita, Osaka, Japan.

Oncogene
|July 21, 2009
PubMed

Insights

Voltage-dependent anion channel 2 (VDAC2) is essential for the pro-apoptotic function of Bax when Bak is absent. VDAC2 deficiency confers resistance to apoptosis, highlighting its critical role in cell death pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondrial membrane permeabilization is a key event in apoptosis, regulated by the Bcl-2 protein family.
  • The precise mechanisms of Bcl-2 family regulation of apoptosis remain incompletely understood.
  • The voltage-dependent anion channel (VDAC) has been implicated in apoptotic mitochondrial outer membrane permeabilization.

Purpose of the Study:

  • To investigate the role of VDAC2 in apoptotic signaling mediated by the Bcl-2 family.
  • To determine if VDAC2 is required for the pro-apoptotic activity of Bax, particularly in the absence of Bak.

Main Methods:

  • Utilized VDAC2-deficient and Bak-deficient cell models.
  • Assessed cellular response to various apoptotic stimuli.
  • Examined Bax activation through mitochondrial membrane integration, conformational changes, and oligomerization.
  • Investigated the effect of VDAC2 gene re-introduction and VDAC2 silencing.

Main Results:

  • VDAC2-deficient cells lacking Bak exhibited significant resistance to apoptotic stimuli.
  • Restoring VDAC2 expression in these cells re-established apoptotic sensitivity.
  • Silencing VDAC2 in Bak-deficient cells, but not Bax-deficient cells, conferred resistance to apoptosis.
  • Bax activation was markedly impaired in cells lacking both VDAC2 and Bak.

Conclusions:

  • VDAC2 is essential for the pro-apoptotic function of Bax when Bak is absent.
  • VDAC2 acts as a critical mediator for Bax-driven apoptosis in specific cellular contexts.
  • These findings elucidate a novel mechanism involving VDAC2 in the regulation of programmed cell death.

More Related Videos

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila13:21

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila

Published on: November 27, 2016

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

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...
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...
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 cells.
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...
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 reduction of the tissue.
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...