Apoptosis describes a genetic program that allows controlled deletion of no longer functional, superfluous or potentially harmful cells. As such, programmed cell death via apoptosis acts as a critical mechanism required for proper organ development during embryogenesis and maintenance of tissue homeostasis in the adult. Importantly, experiments manipulating these signaling pathways demonstrated that apoptosis also acts as a barrier against a variety of heterogeneous diseases including cancer and autoimmunity while excessive apoptosis can promote degenerative disorders as well as immunodeficiency. 

Apoptotic cell death can be induced via one of two main signaling pathways (Figure 1). One is activated upon interaction of certain ligands of the tumor necrosis factor (TNF) family with their cognate receptors, often referred to as death receptors, such as Fas/CD95 or the TNF-receptor itself. Death receptor and ligand mediated cell death fulfills critical roles e.g. in immune cell homeostasis and during responses to infectious agents. A second, more prevalent signaling pathway is controlled by members of the Bcl-2 family and involves mitochondria, hence often also referred to as the mitochondrial pathway to apoptosis. A large variety of developmental signals or cell-stress inducing agents or treatments can activate this cell death pathway, e.g. DNA damage, growth factor deprivation or oncogenic stress, that is of major interest to several groups within the MCBO program.

Fig. 1Apoptosis pathways. The intrinsic pathway (a) is activated by cellular stress and regulated by the Bcl-2 family. The extrinsic pathway (b) requires death-ligand-receptor interaction for its activation. Figure adopted from Tait, S.W.G. and D.R. Green,Nat Rev Mol Cell Biol, 2010

The group of Jakob Troppmair is interested in how oncogenic signals, such as the one emanating from the c-RAF oncogene, a key driver of malignant melanoma in humans, suppresses induction of intrinsic apoptosis and how secondary messengers such as Calcium or reactive oxygen species (ROS) trigger cell death.
The group of Andreas Villunger is mainly interested in how individual Bcl-2 protein family members, in particular BH3-only proteins, control cell death during lymphocyte development and tissue homeostasis to prevent autoimmunity or malignant transformation. A second area of interest deals with the role of an apoptosis-related protease, Caspase-2, in cell death and cell cycle control.

• Andreas Villunger
• Zoran Culig