Bax, Bak and beyond — mitochondrial performance in apoptosis

• Published in: The FEBS journal Vol. 285; no. 3; pp. 416 - 431
• Main Authors: Peña‐Blanco, Aida, García‐Sáez, Ana J.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.02.2018
• Subjects: Animals; Apoptosis; Apoptosis Regulatory Proteins - agonists; Apoptosis Regulatory Proteins - chemistry; Apoptosis Regulatory Proteins - metabolism; BAK; BAX; bcl-2 Homologous Antagonist-Killer Protein - agonists; bcl-2 Homologous Antagonist-Killer Protein - chemistry; bcl-2 Homologous Antagonist-Killer Protein - metabolism; Bcl-2 protein; bcl-2-Associated X Protein - agonists; bcl-2-Associated X Protein - chemistry; bcl-2-Associated X Protein - metabolism; BCL‐2 family; biochemical pathways; biophysics; Dimerization; DRP1; Humans; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Lipid Mobilization; Mitochondria; Mitochondria - chemistry; Mitochondria - enzymology; Mitochondria - metabolism; Mitochondrial Dynamics; Mitochondrial Membranes - chemistry; Mitochondrial Membranes - enzymology; Mitochondrial Membranes - metabolism; mitochondrial outer membrane permeabilization; Models, Biological; Oligomerization; Organelles; Porosity; protein binding; Protein Conformation; Protein Interaction Domains and Motifs; Protein Multimerization; protein structure; Proto-Oncogene Proteins c-bcl-2 - agonists; Proto-Oncogene Proteins c-bcl-2 - chemistry; Proto-Oncogene Proteins c-bcl-2 - metabolism; Regulators; BCL-2 family; mitochondria; BAX; apoptosis; mitochondrial outer membrane permeabilization; BAK; DRP1
• ISSN: 1742-464X; 1742-4658; 1742-4658
• DOI: 10.1111/febs.14186

Bax and Bak are members of the Bcl‐2 family and core regulators of the intrinsic pathway of apoptosis. Upon apoptotic stimuli, they are activated and oligomerize at the mitochondrial outer membrane (MOM) to mediate its permeabilization, which is considered a key step in apoptosis. However, the molecular mechanism underlying Bax and Bak function has remained a key question in the field. Here, we review recent structural and biophysical evidence that has changed our understanding of how Bax and Bak promote MOM permeabilization. We also discuss how the spatial regulation of Bcl‐2 family preference for binding partners contributes to regulate Bax and Bak activation. Finally, we consider the contribution of mitochondrial composition, dynamics and interaction with other organelles to apoptosis commitment. A new perspective is emerging, in which the control of apoptosis by Bax and Bak goes beyond them and is highly influenced by additional mitochondrial components. Bax and Bak are members of the Bcl‐2 family and core regulators of the intrinsic pathway of apoptosis. Here, we review recent structural and biophysical evidence on how Bax and Bak mediate mitochondrial outer membrane permeabilization. We also discuss the regulation of Bax and Bak by the Bcl‐2 family and the contribution of mitochondrial composition and dynamics to apoptosis commitment.