The idea of 'autophagic cell death' has been the subject of some controversy, much of it focused on links between autophagy and apoptosis. In this issue of CDD, Basit et al) report that the chemotherapeutic drug Obatoclax triggers autophagy-dependent cell death, but that this death is RIPK-dependent necroptosis, not apoptosis.Autophagy (also called macroautophagy) is a ubiquitous and evolutionary conserved process of cellular 'self-eating.' During autophagy, multiple cellular signaling cascades converge on the ATG proteins, which mediate the formation of double-membraned vesicles around cytosolic components or organelles. These autophagosomes then fuse with lyso-somes, leading to the breakdown and recycling of their contents. Autophagy is thus a key component of the cellular stress response, allowing the removal of damaged organelles or catabolism of cellular components to generate energy during starvation. Apoptosis is another form of cellular stress response, and in many cases apoptotic cell death is accompanied by upregulation of autophagy. While some studies initially interpreted this as evidence for autophagy directly triggering apoptosis, it is now generally accepted that autophagy is a cytoprotective mechanism that promotes cell survival, and that apoptosis ensues when this protection fails.
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