» Articles » PMID: 24162660

Building Blocks of the Apoptotic Pore: How Bax and Bak Are Activated and Oligomerize During Apoptosis

Overview
Specialty Cell Biology
Date 2013 Oct 29
PMID 24162660
Citations 201
Authors
Affiliations
Soon will be listed here.
Abstract

The central role of the Bcl-2 family in regulating apoptotic cell death was first identified in the 1980s. Since then, significant in-roads have been made in identifying the multiple members of this family, characterizing their form and function and understanding how their interactions determine whether a cell lives or dies. In this review we focus on the recent progress made in characterizing the proapoptotic Bcl-2 family members, Bax and Bak. This progress has resolved longstanding controversies, but has also challenged established theories in the apoptosis field. We will discuss different models of how these two proteins become activated and different 'modes' by which they are inhibited by other Bcl-2 family members. We will also discuss novel conformation changes leading to Bak and Bax oligomerization and speculate how these oligomers might permeabilize the mitochondrial outer membrane.

Citing Articles

Molecular Docking of Lactoferrin with Apoptosis-Related Proteins Insights into Its Anticancer Mechanism.

Angel-Lerma L, Carrillo-Campos J, Sianez-Estrada L, Siqueiros-Cendon T, Leon-Flores D, Espinoza-Sanchez E Int J Mol Sci. 2025; 26(5).

PMID: 40076649 PMC: 11899785. DOI: 10.3390/ijms26052023.


Potential Role of High-Intensity Interval Training-Induced Increase in Humanin Levels for the Management of Type 2 Diabetes.

Soltany A, Daryanoosh F, Gholampour F, Sadat Hossini N, Sadat Hosseini N, Khoramipour K J Cell Mol Med. 2025; 29(3):e70396.

PMID: 39936487 PMC: 11815479. DOI: 10.1111/jcmm.70396.


Hepatocyte Rho-associated kinase signaling is required for mice to survive experimental porphyria-associated liver injury.

Herrera J, Weng Y, Lieberthal T, Paoletti M, Chang T Hepatol Commun. 2025; 9(2).

PMID: 39878679 PMC: 11781774. DOI: 10.1097/HC9.0000000000000636.


Ruthenium(II) Complex with 8-Hydroxyquinoline Exhibits Antitumor Activity in Breast Cancer Cell Lines.

Khalifa A, Sheweita S, Namatalla A, Khalifa M, Nencioni A, Sultan A Cancers (Basel). 2025; 17(2).

PMID: 39857977 PMC: 11763687. DOI: 10.3390/cancers17020195.


Copper-instigated modulatory cell mortality mechanisms and progress in kidney diseases.

Ren X, Zhao L, Hao Y, Huang X, Lv G, Zhou X Ren Fail. 2025; 47(1):2431142.

PMID: 39805816 PMC: 11734396. DOI: 10.1080/0886022X.2024.2431142.


References
1.
Sattler M, Liang H, Nettesheim D, Meadows R, Harlan J, Eberstadt M . Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science. 1997; 275(5302):983-6. DOI: 10.1126/science.275.5302.983. View

2.
Hsu Y, Youle R . Nonionic detergents induce dimerization among members of the Bcl-2 family. J Biol Chem. 1997; 272(21):13829-34. DOI: 10.1074/jbc.272.21.13829. View

3.
Edwards A, Gavathiotis E, LaBelle J, Braun C, Opoku-Nsiah K, Bird G . Multimodal interaction with BCL-2 family proteins underlies the proapoptotic activity of PUMA BH3. Chem Biol. 2013; 20(7):888-902. PMC: 3781208. DOI: 10.1016/j.chembiol.2013.06.007. View

4.
Zhang Z, Zhu W, Lapolla S, Miao Y, Shao Y, Falcone M . Bax forms an oligomer via separate, yet interdependent, surfaces. J Biol Chem. 2010; 285(23):17614-27. PMC: 2878526. DOI: 10.1074/jbc.M110.113456. View

5.
Czabotar P, Westphal D, Dewson G, Ma S, Hockings C, Fairlie W . Bax crystal structures reveal how BH3 domains activate Bax and nucleate its oligomerization to induce apoptosis. Cell. 2013; 152(3):519-31. DOI: 10.1016/j.cell.2012.12.031. View