Related Experiment Video

Updated: May 1, 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

7.4K

MTCH2 promotes BAX and BAK self-assembly and apoptotic pore growth

Hector Flores-Romero1,2,3, Aida Pena-Blanco4, Jonas Aufdermauer1,5

  • 1Institute for Genetics and CECAD, University of Cologne, Cologne, Germany.

Nature Structural & Molecular Biology
|April 29, 2026
PubMed

Insights

Mitochondrial protein MTCH2 promotes the assembly of BAX and BAK during apoptosis. Lacking MTCH2 delays pore formation, impacting cell death and DNA release, crucial for understanding programmed cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Apoptosis involves BAX and BAK oligomerization, forming pores in the mitochondrial outer membrane.
  • The roles of other cellular factors in apoptotic pore dynamics are not fully understood.

Purpose of the Study:

  • To identify cellular components interacting with the apoptotic pore.
  • To elucidate the function of MTCH2 in BAX and BAK assembly and apoptotic pore formation.

Main Methods:

  • In situ proximity labeling to map the protein environment of the apoptotic pore.
  • Single-particle analysis to observe BAX and BAK oligomerization dynamics.
  • Cellular assays to assess apoptosis sensitivity, mitochondrial permeabilization, and DNA release.

Main Results:

  • MTCH2 was identified near BAX and BAK assemblies during apoptosis.
  • MTCH2-deficient cells showed delayed BAX and BAK oligomerization, rescued by lysophosphatidic acid.
  • MTCH2 depletion reduced apoptosis sensitivity, mitochondrial permeabilization, mtDNA release, and cGAS-STING activation.

Conclusions:

  • MTCH2 plays a critical role in promoting BAX and BAK high-order assembly.
  • MTCH2 influences apoptotic pore growth and downstream cellular responses, including innate immune activation.

More Related Videos

Reconstitution of Msp1 Extraction Activity with Fully Purified Components05:52

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Published on: August 10, 2021

2.1K
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

8.5K

Related Concept Videos

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...
6.2K
The Extrinsic Apoptotic Pathway01:17

The 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...
6.2K
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular 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...
99
Caspases01:24

Caspases

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...
8.7K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.1K
Translocation of Proteins into the Mitochondria01:19

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,...
8.8K