The cross talk between autophagy and apoptosis is complex. Autophagy serves as a cytoprotective mechanism in response to stress to generate nutrients during starvation, remove damaged proteins and organelles during metabolic stress, and eliminate intracellular pathogens. Alternatively, autophagy can promote cell death by serving as an independent cell death mechanism or by enabling the induction of apoptosis. While the induction of "autophagic cell death" remains controversial, the molecular cross talk between autophagic and apoptotic pathways is evident and functions to dynamically maintain cellular homeostasis and respond to stress. This chapter summarizes the molecular regulators of the cross talk between apoptosis and autophagy, including the Bcl-2 protein family; mediators of the extrinsic apoptotic pathway; the Beclin 1-interacting molecules Ambra 1 and Bif-1; several autophagy proteins; the transcription factors p53, E2F1, and NF-?B; PI3K/Akt/ mTOR and JNK signal transduction pathways; and microRNAs. Collectively, these molecules function at multiple levels, from direct protein-protein interactions to transcriptional regulation, to control the interplay between apoptosis and autophagy and maintain cellular homeostasis. Molecular mediators of the cross talk between apoptosis and autophagy are continuously being identified; and ultimately, a greater understanding of the cross talk between apoptosis and autophagy will be critical for enhancing the efficacy of anticancer therapies.
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