Related Experiment Video

Updated: Aug 19, 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

Oligomeric Bax is a component of the putative cytochrome c release channel MAC, mitochondrial apoptosis-induced

Laurent M Dejean1, Sonia Martinez-Caballero, Liang Guo

  • 1Department of Basic Sciences, College of Dentistry, New York University, New York, NY 10010, USA.

Molecular Biology of the Cell
|March 18, 2005
PubMed

Insights

The study reveals that Bax is a key component of the mitochondrial apoptosis-induced channel (MAC), crucial for releasing cytochrome c during programmed cell death. Bax and Bak proteins appear functionally redundant in forming this channel.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The Bcl-2 protein family regulates apoptosis by controlling the formation of the mitochondrial apoptosis-induced channel (MAC).
  • MAC is a putative channel for cytochrome c release, a critical event in the intrinsic apoptotic pathway.
  • Channel activity is absent in Bcl-2-overexpressing cells and appears during Bax translocation to mitochondria.

Purpose of the Study:

  • To investigate the role of Bax in the formation and function of the MAC.
  • To determine if Bax is a component of the MAC and how it relates to channel activity.
  • To explore the functional redundancy of Bax and Bak in MAC formation.

Main Methods:

  • Immunodepletion of MAC activity using Bax antibodies in staurosporine-treated HeLa cells.
  • Analysis of MAC association with oligomeric versus monomeric Bax.
  • Comparison of single-channel behavior of recombinant oligomeric Bax and MAC.
  • Measurement of mitochondrial patch conductance before and after Bax translocation.
  • Assessment of MAC activity in cells deficient in Bax and/or Bak.

Main Results:

  • Bax antibodies immunodeplete MAC activity, confirming Bax as a MAC component.
  • MAC activity is preferentially associated with oligomeric Bax, and its channel behavior resembles recombinant oligomeric Bax.
  • Mitochondrial patch conductance increases significantly after green fluorescent protein-Bax translocation.
  • MAC activity is present in apoptotic cells lacking Bax but absent in cells lacking both Bax and Bak.

Conclusions:

  • Bax is a component of the MAC in staurosporine-treated HeLa cells.
  • Bax and Bak likely function redundantly as components of the MAC.
  • These findings elucidate the molecular composition and regulation of the MAC in intrinsic apoptosis.

More Related Videos

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

F1FO ATPase Vesicle Preparation and Technique for Performing Patch Clamp Recordings of Submitochondrial Vesicle Membranes08:21

F1FO ATPase Vesicle Preparation and Technique for Performing Patch Clamp Recordings of Submitochondrial Vesicle Membranes

Published on: May 4, 2013

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...
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...
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.
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.
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...
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...