In the basal phylum Cnidaria, the initiation of cell death has been shown to occur during development, hyperthermic stress, ultraviolet radiation, chemical induction immune response to disease and onset of symbiosis. The apoptotic pathway is dependent upon the activation of proteolytic enzymes named caspases. Caspase activation can be initiated through either the extrinsic pathway or the intrinsic pathway which involves the permeabilisation of the mitochondrial outer membrane and subsequent release of 
cytochrome c into the cytosol. The regulation of the mitochondria intrinsic pathway is Ginsenoside-F2 performed by a Tulathromycin B complex protein network in which the B-cell lymphoma protein-2 family members form a central checkpoint that determines whether a cell lives or dies. Bcl-2 proteins are divided between pro-apoptotic and antiapoptotic members according to their Bcl-2 Homology domains and associated function. Among the pro-apoptotic members, Bcl-2-associated X and Bcl-2antagonist/killer-1 promote apoptosis through their oligomerization and insertion in the mitochondrial outer membrane where they form large pores. Bax and Bak activation is controlled by the interplay and heterodimer formation with antiapoptotic members, such as Bcl-2. Bcl-2 is potentially the most characterised anti-apoptotic member, and functions by regulating transcription, caspase activation, mitochondrial membrane pore formation, intracellular Ca2+ homeostasis and by increasing cellular resistance to oxidative stress. Consequently, it has been suggested that the ratios between antiapoptotic Bcl-2 and pro-apoptotic Bax and Bak may be more important than either promoter alone in determining apoptosis. These ratios can therefore be used as prognostic markers to study apoptosis regulation. Although direct evidence of mitochondrial outer membrane permeabilisation is still lacking in the more basal phyla, extensive studies have revealed that the general outline of the apoptotic machinery is conserved among metazoans. In the Cnidaria, a basal metazoan phylum, both anti-apoptotic and pro-apoptotic-like Bcl-2 sequences have been identified in the hydrozoan Hydra magnipapillata, the non-symbiotic anthozoan, Nematostella vectensis, the symbiotic anthozoans Aiptasia pulchella and the reef building corals Acropora aspera and A. millepora. Furthermore, there is now increasing evidence that activation of caspase-dependent apoptosis plays a role during cnidarian bleaching. However, a direct link between the molecular regulation of the Bcl-2 family of apoptotic mediators and the activation of cell death in corals is still yet to be shown. The present study aimed to provide an integrated picture of the regulation of the mitochondrial apoptotic cascade by Bcl-2 family members within the reef building coral A. millepora. In this respect, we used quantitative Real-Time PCR to monitor the potential initiation of apoptosis by differential expression of Bcl-2, Bax and Bak, fluorometric assay of downstream caspase 3-like activity to measure the execution of apoptotic events and TUNEL labelling to detect the completion of cell death via DNA fragmentation. Regulation of these apoptotic mediators was investigated in complement to indicators of coral bleaching in response to defined stressors and different thermal treatments. This work aims to bring further insight into the characterization of the apoptotic pathways and their functional activation in symbiotic Cnidaria during thermal stress. Deciphering the cellular and molecular mechanisms that determine the sensitivity of corals to thermal stress represents an important step to predicting and understanding the impacts of climate change on coral reefs. In this respect, apoptosis is an important and fundamental component of the response of corals to thermal stress. Indeed, several studies focusing either on functional activation of apoptosis or transcriptomics in Cnidaria have separately demonstrated the involvement of apoptosis in response to rising seawater temperature.