Caspase-8 and BID Caught in the Act with Cardiolipin: A New Platform to Provide Mitochondria with Microdomains of Apoptotic Signals.

Mitochondria play a central role in cellular bioenergetics. They contribute significantly to ATP production, which is essential for maintaining cells. They are also key mediators of various types of cell death, including apoptosis, necroptosis, and ferroptosis. Additionally, they are one of the main regulators of autophagy. This brief review focuses on BID, a molecule of the BCL-2 family that is often overlooked. The importance of the cardiolipin/caspase-8/BID-FL platform, which is located on the surface of the outer mitochondrial membrane and generates tBID, will be emphasized. tBID is responsible for BAX/BAK delocalization and oligomerization, as well as the transmission of death signals. New insights into the regulation of caspase-8 and BID have emerged, and this review will highlight their originality in the context of activation and function. The focus will be on results from biophysical studies of artificial membranes, such as lipid-supported monolayers and giant unilamellar vesicles containing cardiolipin. We will present the destabilization of mitochondrial bioenergetics caused by the insertion of tBID at the mitochondrial contact site, as well as the marginal but additive role of the MTCH2 protein, not forgetting the new players.