Bax, Bak and beyond - mitochondrial performance in apoptosis

Aida Peña-Blanco1, Ana J García-Sáez1,2

  • 1Interfaculty Institute of Biochemistry, Tübingen University, Germany.

The FEBS Journal
|July 30, 2017
PubMed

Insights

Bax and Bak proteins initiate programmed cell death by permeabilizing the mitochondrial outer membrane. Recent evidence reveals their function is influenced by mitochondrial context and interactions with other proteins.

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Bax and Bak are key regulators of the intrinsic apoptosis pathway.
  • They oligomerize at the mitochondrial outer membrane (MOM) to induce permeabilization during apoptosis.
  • The precise molecular mechanisms of Bax and Bak function remain incompletely understood.

Purpose of the Study:

  • To review recent structural and biophysical evidence elucidating Bax and Bak function.
  • To discuss the role of spatial regulation and binding partner interactions in Bax and Bak activation.
  • To explore the influence of mitochondrial composition, dynamics, and organelle interactions on apoptosis.

Main Methods:

  • Review of structural biology data.
  • Analysis of biophysical studies.
  • Integration of findings on Bcl-2 family interactions and mitochondrial regulation.

Main Results:

  • New structural and biophysical insights into Bax and Bak-mediated MOM permeabilization.
  • Understanding of how spatial regulation of Bcl-2 family binding partners controls Bax and Bak activation.
  • Recognition of the broader mitochondrial context influencing apoptosis.

Conclusions:

  • Apoptosis regulation by Bax and Bak is more complex than previously thought.
  • Mitochondrial composition, dynamics, and inter-organelle interactions are critical for apoptosis commitment.
  • A holistic view integrating Bax, Bak, and mitochondrial environment is essential for understanding apoptosis.

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...
8.8K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
16.0K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.7K
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...
14.3K
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...
9.0K
Mitochondrial Membranes01:45

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,...
17.5K