Crosstalk between apoptosis, necrosis and autophagy

Abstract

Apoptosis and necrosis are the two major modes of cell death, the molecular mechanisms of which have been extensively studied. Although initially thought to constitute mutually exclusive cellular states, recent findings reveal cellular contexts that require a balanced interplay between these two modes of cellular demise. Several death initiator and effector molecules, signaling pathways and subcellular sites have been identified as key mediators in both processes, either by constituting common modules or alternatively by functioning as a switch allowing cells to decide which route to take, depending on the specific situation. Importantly, autophagy, which is a predominantly cytoprotective process, has been linked to both types of cell death, serving either a pro-survival or pro-death function. Here we review the recent literature that highlights the intricate interplay between apoptosis, necrosis and autophagy, focusing on the relevance and impact of this crosstalk in normal development and in pathology. This article is part of a Special Section entitled: Cell Death Pathways.

Keywords: AIF; AMPK; APAF1; Adenosine Monophosphate activated Kinase; Apoptosis; Apoptosis Inducing Factor; Apoptotic Protease Activating Factor 1; Autophagy; B-cell lymphoma 2; B-cell lymphoma extra large; BCL-2; BCL-X(l); BEC1; BH; Bcl-2 homology; Beclin-1; Cell death; DAPK; DRAM; Damage-Regulated Autophagy Modulator; FADD; FAS Associated Death Domain; FLICE; FLICE-Like Inhibitory Protein; FLIP; FOXO1; Forkhead Box Protein O1; HDGF; HMGB1; Hepatoma Derived Growth Factor; High Mobility Group protein B1; IGF1; IL1β; Insulin Growth Factor 1; LKB1; Liver Kinase B1; MEFs; MNNG; MOMP; Mitoptosis; N-methyl-N0-nitrosoguanidine; NEMO; NF-kB; NF-kB essential modulator; NLRP3; NOD-like receptor family pyrin domain containing 3; Necroptosis; Necrosis; Nuclear factor kappa-light-chain-enhancer of activated B cells; PAMP; PARP1; PCD; PI3K; PRR; PTP; PUMA; Pathogen Associated Molecular Patterns; Phosphatidyl Inositol 3 Kinase; Poly(ADP ribose) Polymerase 1; RIP1; RIP3; Receptor Interacting Protein 1; Receptor Interacting Protein 3; SIRT2; Sirtuin 2; TNF related apoptosis inducing ligand; TNFR Associated Death Domain; TNFR Associated Factor 2; TNFR Associated Factor 5; TNFR1; TNFR2; TNFα; TNFα Receptor 1; TNFα receptor 2; TRADD; TRAF2; TRAF5; TRAIL; TRAIL Receptor 1; TRAIL Receptor 2; TRAILR1; TRAILR2; Tumor Necrosis Factor alpha; cIAP1; cIAP2; caspase 8; cellular inhibitor of apoptosis 1; cellular inhibitor of apoptosis 2; death associated protein kinase; interleukin 1β; mTOR; mammalian target of rapamycin; mitochondrial outer membrane permeabilization; mouse embryonic fibroblasts; p53-Upregulated Modulator of Apoptosis; pathogen recognition receptor; permeability transition pore; programmed cell death; tAIF; truncated Apoptosis Inducing Factor.