Autophagy and apoptosis are catabolic pathways essential for organismal homeostasis. Autophagy is normally a cell-survival pathway involving the degradation and recycling of obsolete, damaged, or harmful macromolecular assemblies; however, excess autophagy has been implicated in type II cell death. Apoptosis is the canonical programmed cell death pathway. Autophagy and apoptosis have now been shown to be interconnected by several molecular nodes of crosstalk, enabling the coordinate regulation of degradation by these pathways. Normally, autophagy and apoptosis are both tumor suppressor pathways. Autophagy fulfils this role as it facilitates the degradation of oncogenic molecules, preventing development of cancers, while apoptosis prevents the survival of cancer cells. Consequently, defective or inadequate levels of either autophagy or apoptosis can lead to cancer. However, autophagy appears to have a dual role in cancer, as it has now been shown that autophagy also facilitates the survival of tumor cells in stress conditions such as hypoxic or low-nutrition environments. Here we review the multiple molecular mechanisms of coordination of autophagy and apoptosis and the role of the proteins involved in this crosstalk in cancer. A comprehensive understanding of the interconnectivity of autophagy and apoptosis is essential for the development of effective cancer therapeutics. 1. Introduction to Autophagy Autophagy is a cell-survival pathway conserved in all eukaryotes. It involves the selective degradation of cellular components, including long-lived proteins, protein aggregates, damaged cytoplasmic organelles, and intracellular pathogens, resulting in the recycling of nutrients and the generation of energy [1]. Basal levels of autophagy are required for cellular homeostasis. Autophagy is upregulated under stress conditions, including extracellular stress such as nutrition deprivation, hypoxia, and infection and intracellular stress such as that caused by accumulation of damaged proteins and organelles and high bioenergetic demands. It allows lower eukaryotes to survive starvation, while in mammals, it is thought to be involved in many physiological and pathophysiological processes, including antiaging mechanisms, differentiation and development, immunity, and elimination of microorganisms [2–9]. Autophagy is a highly regulated process (Figure 1) executed by autophagy-related effectors, many of which are called ATG proteins [1, 6, 10]. The first committed step of autophagy is vesicle nucleation in which macromolecular assemblies selected for degradation
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