Related Experiment Video
Updated: Aug 8, 2026
08:35
Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Ultrastructural localization of bcl-2 protein
P Monaghan1, D Robertson, T A Amos
1Department of Cell Biology and Experimental Pathology, Institute of Cancer Research, Sutton, Surrey, UK.
Summary
The BCL-2 protein, previously thought to be in the inner mitochondrial membrane, is found on the outer mitochondrial membrane in lymphoma and breast cancer cells. This study reveals its presence at multiple cellular locations.
Area of Science:
- Cell Biology
- Oncology
- Biochemistry
Background:
- Previous cell subfractionation studies suggested BCL-2 localizes to the inner mitochondrial membrane.
- Overexpression of BCL-2 is common in various cancers, including lymphoma and breast carcinoma.
Purpose of the Study:
- To determine the ultrastructural localization of BCL-2 protein in cancer cell lines and biopsy samples.
- To investigate BCL-2 localization using multiple sample preparation methods to minimize processing artifacts.
Main Methods:
- Immunoelectron microscopy was employed to visualize BCL-2 protein.
- Three distinct sample preparation techniques were utilized: progressive lowering of temperature, cryosectioning, and freeze-substitution.
- Confocal microscopy was used for corroborative cytoplasmic and perinuclear membrane localization.
Main Results:
- BCL-2 protein labeling was observed on the periphery of mitochondria in both lymphoma and breast carcinoma tissues.
- Minimal BCL-2 labeling was detected within the mitochondrial matrix or on the cristae.
- Labeling was also present on the perinuclear membrane and throughout the cytoplasm.
- Contrary to prior expectations, BCL-2 protein showed a preferential association with the outer mitochondrial membrane.
Conclusions:
- BCL-2 protein localizes to multiple intracellular sites, including the outer mitochondrial membrane, perinuclear membrane, and cytoplasm.
- The findings challenge the established view of BCL-2 as solely an inner mitochondrial membrane protein.
- This revised understanding of BCL-2 localization may have implications for its role in cancer biology and therapeutic strategies.
More Related Videos
Related Concept Videos
02:55The Nucleolus
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
01:38Intralumenal Vesicles and Multivesicular Bodies
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
01:34Nuclear Protein Sorting
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
01:46Nuclear Localization Signals and Import
Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of 2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:27Post-translational Translocation of Proteins to the RER
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...