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Related Experiment Video

Updated: May 23, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

Bax regulates primary necrosis through mitochondrial dynamics.

Russell S Whelan¹, Klitos Konstantinidis, An-Chi Wei

¹Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Proceedings of the National Academy of Sciences of the United States of America

|April 12, 2012

Summary

Bcl-2 proteins Bax and Bak unexpectedly protect against necrotic injury by promoting mitochondrial fusion, which lowers the threshold for mitochondrial permeability transition pore (mPTP) opening and necrosis.

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Live-cell Imaging of Lysosomal Membrane Permeabilization During Necroptosis

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Published on: November 14, 2025

Area of Science:

Cellular biology
Mitochondrial dynamics
Cell death pathways

Background:

Apoptosis is triggered by mitochondrial outer membrane permeabilization (MOMP), while necrosis involves mitochondrial inner membrane permeability transition pore (mPTP) opening.
Bcl-2 proteins Bax and Bak are known activators of MOMP and apoptosis.

Purpose of the Study:

To investigate the role of Bax and Bak in necrotic injury, particularly during myocardial infarction.
To elucidate the mechanisms by which Bax and Bak influence cell death pathways.

Main Methods:

Utilized knockout mice lacking Bax/Bak and cyclophilin D.
Examined isolated mitochondria and cell cultures.
Investigated the effects of Bax reconstitution and mitofusin 2 (Mfn2) deficiency.
Assessed mitochondrial fusion and fission dynamics.

Main Results:

Deletion of Bax and Bak significantly reduced necrotic injury in myocardial infarction models.
Bax/Bak-deficient cells and mitochondria were resistant to mPTP opening and necrosis.
Reconstitution with Bax restored mPTP opening and necrosis, independent of MOMP.
Bax and Mfn2 promoted mitochondrial fusion, and a fused mitochondrial state was critical for mPTP opening and necrosis.

Conclusions:

Bax and Bak play a previously unrecognized role in promoting necrosis by driving mitochondrial fusion.
Bax-driven mitochondrial fusion lowers the threshold for mPTP opening, thus facilitating necrosis.
Bax and Bak are potential therapeutic targets for diseases involving both apoptosis and necrosis.