Organelle Cross-Talk in Apoptotic and Survival Pathways

Apoptosis and survival pathways are intimately connected signal transduction cascades that determine the fate of cells suffering from insults such as DNA damage, oxidative stress, intracellular Ca 2+ overload, mild excitotoxicity, accumulation of unfolded or misfolded proteins in the endo-plasmic reticulum (ER), and many others, or induced to autoelimination by extracellular signals. The apoptotic pathways , respectively, intrinsic or extrinsic, are executed through molecular signals travelling inside the cells. If the initial studies considered the nucleus, and specifically DNA, as both primary sensor and executioner of apoptosis, active roles of other intracellular organelles have been pointed out in the last two decades, identifying plasma membrane as the initiator of the extrinsic pathway and mitochondria as the pivot of the intrinsic pathway. In apoptosing cells, the outer membrane of mitochondria is permeabilized by the proapo-ptotic members of the Bcl-2 family, promoting the release of proapoptotic factors such as the primary and secondary acti-vators of caspases (cytochrome c and SMAC/diablo, resp.). Stress signals, typically inducing the intrinsic apoptotic pathway , must be perceived by the damaged cells and translated into signals that promote mitochondria permeabilization, after which caspases are activated. This implies that other organelles participate in apoptotic signaling upstream to mitochondria involvement, acting as sensors of damage or signal transducers. Recently, a key role of the endoplasmic reticulum (ER) is emerging, consisting of the ability of amplifying or dampening the apoptotic signal prior to mitochondria involvement, through the establishment of active Ca 2+ fluxes that control the physical and functional interaction between mitochondria and ER. Also lysosomes participate to the intrinsic apoptotic signaling, and their dialogs with mitochondria have been described. Other important examples of organelles cross-talk in apoptosis include nucleus-mitochondria exchange of proteins such as p53, which is main controller of the cell response to DNA damage. To date, the role of organelles other than mito-chondria in perceiving and signaling cell damage, and the interrelation of the organelles during apoptotic signaling, are still poorly explored matters. In this special issue dedicated to Organelle Cross-talk in Apoptotic and Survival Pathways, original research papers and review articles are collected with the aim of giving an impulse to this promising field of research on apoptosis and stimulating discussion between interdisciplinary readers. The paper written by Y.-B. Ouyang and R. G. Gif-fard describes ER-mitochondria cross-talk during cerebral ischemia. The authors precisely describe the chaperone machineries at both the ER and mitochondrion. Moreover, they contribute …