Related Experiment Video

Updated: Aug 9, 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

The BCL-2 family of proteins and mitochondrial outer membrane permeabilisation

Richard W Birkinshaw1, Peter E Czabotar1

  • 1The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.

Seminars in Cell & Developmental Biology
|April 12, 2017
PubMed

Insights

Programmed cell death, or apoptosis, involves mitochondrial outer membrane permeabilization (MOM) regulated by BCL-2 family proteins. Understanding these interactions and structural changes in BAK and BAX is key for developing cancer therapeutics.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Apoptosis is programmed cell death essential for organism development and homeostasis.
  • Mitochondrial outer membrane permeabilization (MOM) is a critical, irreversible step in apoptosis.
  • The BCL-2 protein family regulates MOM permeabilization through complex interactions.

Purpose of the Study:

  • To review the roles of opposing factions within the BCL-2 family.
  • To detail the structural mechanisms governing BCL-2 interactions.
  • To explore conformational changes in BAK and BAX leading to MOM permeabilization.

Main Methods:

  • Review of existing literature on BCL-2 family interactions.
  • Analysis of structural data related to BCL-2 proteins.
  • Discussion of recent findings on BAK and BAX conformational dynamics.

Main Results:

  • The BCL-2 family comprises pro-apoptotic and anti-apoptotic members with distinct interaction domains.
  • Structural insights reveal how BCL-2 interactions promote or inhibit MOM permeabilization.
  • Conformational changes in BAK and BAX are crucial for initiating MOM permeabilization.

Conclusions:

  • Understanding BCL-2 family interactions and protein structures is vital for regulating apoptosis.
  • Targeting BCL-2 family members offers therapeutic potential for diseases involving dysregulated apoptosis, such as cancer.
  • Structural studies provide a foundation for rational drug design to restore apoptosis in cancer cells.
Keywords:
ApoptosisBAKBAXBCL-2 family proteinsMitochondrial outer membrane permeabilisationOligomers

More Related Videos

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

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess07:35

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess

Published on: June 1, 2022

Related Concept Videos

Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
The Inner Mitochondrial Membrane01:28

The Inner Mitochondrial Membrane

The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria.  In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
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...
Structure of Porins01:21

Structure of Porins

Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel precursors...