Organelle dynamics and membrane trafficking in apoptosis and autophagy

Abstract

The accurate control of cell death is a vital aspect of development in metazoans and plays crucial roles in the prevention of disease. Apoptosis is the main form of regulated cell death in multicellular organisms, although there are other contributory pathways. During apoptosis, mammalian cells undergo dramatic changes in organelle structure ad organisation that define the apoptotic execution phase. Although the roles of apoptotic protease machinery (the caspases) in these rearrangements are quite well understood, the purpose of organelle disruption during cell death is not yet entirely appreciated. Indeed, recent evidence implicates caspase targeting of organellar proteins and subsequent organelle disruption upstream of apoptotic execution proper, suggesting the existence of pathways linking organelle damage to cell death. In this review, we describe the changes to the endomembrane system that are inherent during the apoptotic execution phase, and examine the evidence for endomembrane-mediated pathways towards apoptotic execution. We also discuss aspects of the molecular control of autophagy - an important contributor to a cell’s response to stress, and a membrane trafficking process whose regulation is linked to the apoptotic machinery at multiple levels.