Molecular machinery and signaling events in apoptosis

Apoptosis is a process of major biomedical interest, since its ineffectiveness or inappropriate activation appears to be involved in the pathogenesis of a broad variety of human diseases (neoplasia, autoimmune disorders, viral and neurodegenerative diseases, to name a few). On this topic, extensive experimental work has allowed in the past years the clarification of the complex biochemical machinery that commits a cell to apoptosis and executes the death program. As to the signalling mechanisms, it is now evident that apoptosis can be initiated by different stimuli and/or genetic programs, that are differentially decoded inside the cell. While the past years have witnessed a major advancement also on this topic, much still needs to be learnt on the cross-talk between the various signalling pathways involved in decoding the apoptotic stimuli, as well as the activation of other cell functions. In this review, we will first describe the properties and activation mechanisms of the caspases, the effector proteases of apoptosis. In the second part, we will discuss the current evidence for the involvement of calcium, the ubiquitous second messenger decoding a wide variety of physiological stimuli, and highlight the potential targets of the apoptotic calcium signal.