Apoptotic mitochondrial poration by a growing list of pore-forming BCL-2 family proteins.
Tudor MoldoveanuPublished in: BioEssays : news and reviews in molecular, cellular and developmental biology (2023)
The pore-forming BCL-2 family proteins are effectors of mitochondrial poration in apoptosis initiation. Two atypical effectors-BOK and truncated BID (tBID)-join the canonical effectors BAK and BAX. Gene knockout revealed developmental phenotypes in the absence the effectors, supporting their roles in vivo. During apoptosis effectors are activated and change shape from dormant monomers to dynamic oligomers that associate with and permeabilize mitochondria. BID is activated by proteolysis, BOK accumulates on inhibition of its degradation by the E3 ligase gp78, while BAK and BAX undergo direct activation by BH3-only initiators, autoactivation, and crossactivation. Except tBID, effector oligomers on the mitochondria appear as arcs and rings in super-resolution microscopy images. The BH3-in-groove dimers of BAK and BAX, the tBID monomers, and uncharacterized BOK species are the putative building blocks of apoptotic pores. Effectors interact with lipids and bilayers but the mechanism of membrane poration remains elusive. I discuss effector-mediated mitochondrial poration.
Keyphrases
- type iii
- cell death
- oxidative stress
- induced apoptosis
- cell cycle arrest
- endoplasmic reticulum stress
- dendritic cells
- optical coherence tomography
- regulatory t cells
- genome wide
- single molecule
- high throughput
- machine learning
- reactive oxygen species
- molecular dynamics simulations
- convolutional neural network
- high speed
- cell proliferation
- single cell
- label free
- genetic diversity