Heat Shock Protein 70 Promotes Cell Survival by Inhibiting Lysosomal Membrane Permeabilization

Heat shock protein 70 (Hsp70) is a potent survival protein whose depletion triggers massive caspase-independent tumor cell death. Here, we show that Hsp70 exerts its prosurvival function by inhibiting lysosomal membrane permeabilization. The cell death induced by Hsp70 depletion was preceded by the release of lysosomal enzymes into the cytosol and inhibited by pharmacological inhibitors of lysosomal cysteine proteases. Accordingly, the Hsp70-mediated protection against various death stimuli in Hsp70-expressing human tumor cells as well as in immortalized Hsp70 transgenic murine fibroblasts occurred at the level of the lysosomal permeabilization. On the contrary, Hsp70 failed to inhibit the cytochrome c–induced, apoptosome-dependent caspase activation in vitro and Fas ligand–induced, caspase-dependent apoptosis in immortalized fibroblasts. Immunoelectron microscopy revealed that endosomal and lysosomal membranes of tumor cells contained Hsp70. Permeabilization of purified endo/lysosomes by digitonin failed to release Hsp70, suggesting that it is physically associated with the membranes. Finally, Hsp70 positive lysosomes displayed increased size and resistance against chemical and physical membrane destabilization. These data identify Hsp70 as the first survival protein that functions by inhibiting the death-associated permeabilization of lysosomes

Intracellular Signaling: Peripatetic Ras

SummaryRas proteins traffic between the plasma membrane and endomembranes and signal from the cytosolic face of a variety of organelles. Palmitoylated N-Ras and H-Ras signal from early endosomes. A recent study reports that K-Ras resides on and signals from various types of endosomes, including late endosomes/lysosomes and multivesicular bodies

Carbon integration and transfer by the photosynthetic symbiotic dinoflagellates of the planktonic foraminifer Orbulina universa observed by TEM-nanoSIMS techniques

The planktonic foraminifera Orbulina universa is living in the photic zone of marine water columns and it possesses photosynthetic microalgae symbionts in its cytoplasm (dinoflagellates). The transfer of carbon compounds from the symbiotic microalgae to the foraminifer host cell is a continuous process. During day microalgae might migrate on the spines to start to transfer carbon compounds from their starch vesicles to the lipid droplets of the foraminifer. During night, nearly the total amount of photoassimilates accumulated during the light phase is transferred from the symbiont starch vesicles to the host lipid droplets