Related Experiment Video
Updated: May 11, 2026
08:35
Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Traveling Bax and forth from mitochondria to control apoptosis
Maria Eugenia Soriano1, Luca Scorrano
1Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy.
Cell
|April 5, 2011
Summary
Antiapoptotic Bcl-2 proteins prevent cell death by inhibiting prodeath proteins like Bax. New research shows Bax and Bcl-xL interact on mitochondria, then move to the cytosol to block cell death.
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- Antiapoptotic B-cell lymphoma 2 (Bcl-2) proteins reside on mitochondria, inhibiting prodeath proteins such as Bax, which is primarily located in the cytosol.
- Mitochondrial outer membrane permeabilization (MOMP) is a critical step in apoptosis, regulated by the balance between Bcl-2 proteins and proapoptotic proteins.
Discussion:
- Edlich et al. demonstrate that Bax and Bcl-extra-large (Bcl-xL) interact at the mitochondrial surface.
- Following interaction, Bax and Bcl-xL retrotranslocate to the cytosol.
- This translocation effectively prevents Bax-induced mitochondrial permeabilization.
Key Insights:
- Bcl-xL can sequester Bax on the mitochondrial surface.
- The interaction and subsequent retrotranslocation of Bax and Bcl-xL represent a novel mechanism for regulating apoptosis.
- This finding challenges the prevailing model of Bax activation solely at the mitochondria.
Outlook:
- Further investigation into the precise mechanisms of Bax-Bcl-xL interaction and retrotranslocation.
- Exploring the therapeutic potential of modulating this interaction in diseases involving aberrant apoptosis.
- Understanding the role of other Bcl-2 family members in this newly identified regulatory pathway.
Related Concept Videos
01:19Translocation 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,...
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,...
01:30Apoptosis
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.
01:24Caspases
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.
01:17The 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...
01:31The 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...
01:22Cellular 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...