Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

The Intrinsic Apoptotic Pathway

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 Porins

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...

Porin Insertion in the Outer Mitochondrial Membrane

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...

Translocation of Proteins into the Mitochondria

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,...

Mitochondrial Protein Sorting

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...

Mitochondrial Membranes

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,...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Beyond the veil of cell death.

Cell chemical biology·2026

Same author

Cytokines driven by caspase-1 and RIPK3 are antagonistic.

bioRxiv : the preprint server for biology·2026

Same author

Author Correction: cBAF complex components and MYC cooperate early in CD8<sup>+</sup> T cell fate.

Nature·2026

Same author

The mannosyltransferase DPM1 regulates the activity of ER-stress sensor IRE1 in colorectal cancer.

Nature communications·2026

Same author

Autophagy modulation in cancer.

Nature reviews. Drug discovery·2026

Same author

ISG15 negatively regulates RIPK3-mediated cell death and viral pathogenesis.

Cell reports·2026

Search research articles

Related Experiment Video

Updated: Jul 7, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

How do BCL-2 proteins induce mitochondrial outer membrane permeabilization?

Jerry E Chipuk¹, Douglas R Green

¹St Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA.

Trends in Cell Biology

|March 4, 2008

Summary

BH3-only proteins initiate mitochondrial outer membrane permeabilization (MOMP) by both directly activating BAX/BAK and neutralizing inhibitory BCL-2 proteins. This dual action is crucial for efficient apoptosis.

More Related Videos

Immunodetection of Outer Membrane Proteins by Flow Cytometry of Isolated Mitochondria

Immunodetection of Outer Membrane Proteins by Flow Cytometry of Isolated Mitochondria

Published on: September 18, 2014

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

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

Published on: June 1, 2022

Related Experiment Videos

Last Updated: Jul 7, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

Immunodetection of Outer Membrane Proteins by Flow Cytometry of Isolated Mitochondria

Immunodetection of Outer Membrane Proteins by Flow Cytometry of Isolated Mitochondria

Published on: September 18, 2014

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

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

Published on: June 1, 2022

Area of Science:

Cellular biology
Molecular biology
Biochemistry

Background:

Apoptosis, or programmed cell death, is essential for development and tissue homeostasis.
The mitochondrial pathway of apoptosis involves the release of molecules from mitochondria to the cytosol.
Mitochondrial outer membrane permeabilization (MOMP) is a critical step in this pathway, regulated by the BCL-2 protein family.

Purpose of the Study:

To investigate the precise mechanism by which BH3-only proteins initiate MOMP.
To address the ongoing debate regarding the roles of BH3-only proteins in apoptosis regulation.
To propose a unified model for BH3-only protein function in MOMP.

Main Methods:

Review and synthesis of existing literature on BCL-2 family interactions.
Analysis of experimental evidence supporting different models of MOMP initiation.
Theoretical modeling of BH3-only protein function.

Main Results:

The study evaluates two primary models for BH3-only protein function: direct activation of BAX/BAK versus neutralization of anti-apoptotic BCL-2 proteins.
Evidence suggests that BH3-only proteins likely engage in both direct activation and neutralization.
A dual-function model is proposed as necessary for efficient MOMP.

Conclusions:

BH3-only proteins play a dual role in initiating MOMP.
Efficient apoptosis requires BH3-only proteins to both directly engage BAX/BAK and neutralize anti-apoptotic BCL-2 proteins.
This dual mechanism ensures robust control over the mitochondrial apoptosis pathway.