Molecular Cell Biology of Apoptosis in Health and Disease

Apoptotic cell death is fundamental to the life of multicellular organisms, making central contributions to processes ranging from embryonic development to tissue homeostasis. Two distinct apoptosis pathways have been defined: extrinsic apoptosis and mitochondrial apoptosis. As we discuss, apoptosis is an evolutionary conserved process that is, unsurprisingly, tightly regulated. Inhibition of apoptosis can promote cancer, whereas inappropriate apoptosis has been associated with various neurodegenerative diseases. At its core, apoptosis is initiated and executed by proteases called caspases that, once activated, rapidly dismantle dying cells, ensuring that apoptosis is immunologically silent. In this chapter, we discuss the molecular mechanisms of apoptosis and its evolutionary conservation. Secondly, we highlight the emerging concept that apoptosis signalling can be engaged at non-lethal levels with diverse biological effects. Finally, we provide an overview of how apoptosis can impact health and disease, discussing ways in which apoptosis can be therapeutically targeted.