Fusion fuels killing

n page 987, Yu et al. identify a novel cell death pathway that bypasses mito-chondria. The results indicate that various strategies exist to kill off neurons. A lot of the killing of sympathetic neurons occurs in the first week after birth. During that paring period, ‫ف‬ 50% of sympathetic neurons die due to a lack of nerve growth factor (NGF). Neurons deprived of NGF in vitro die through the classical cell death pathway, which includes the release of cytochrome c from mitochondria and the O Mitochondria are intact in neurons dying from GDNF deprivation. resulting activation of caspases. Other factors can also promote neuronal survival, but it now seems that the method used to kill cells after withdrawal of these factors is not the same. Yu et al. find that depriving sympathetic neurons in vitro of GDNF kills cells without mitochondrial involvement. Different caspases were activated than in NGF-dependent neurons, cytochrome c was not released, and mitochondrial structure was maintained in GDNF-deprived neurons. Initiation of this pathway probably involves the GDNF receptor Ret, which may activate caspase-2 when GDNF is absent. Whether certain neurons depend solely on GDNF for survival in vivo remains to be seen. Perhaps the mitochondria-independent pathway is only a backup in case the main system fails. But if death pathways are factor-and cell type–specific, some neuronal death might be blocked selectively by interfering with one but not another death pathway. ᭿ n page 1123, Hernandez et al. demonstrate that a human bacterial pathogen makes host defense cells self-destruct by engulfing their own organelles. This engulfment, known as autophagy, is commonly used by eukaryotic cells to remove damaged organelles by enveloping them in membranes (probably derived from the ER) that later fuse with lysosomes. High levels of autophagy is also a form of programmed cell death—a process that the bacterium Salmonella is now shown to hijack. O Macrophages infected by Salmonella accumulate vesicles that resemble autophagosomes. The authors show that the Salmonella protein SipB is all the bacteria need to get autophagy rolling. SipB is a translocase that sends pathogenic effector proteins into host cells. The authors show that SipB also functions within the infected cell, where it finds its way to mitochondria. There, SipB's demonstrated fusion activity may explain the appearance of damaged and bloated mitochondria, which then become a target for the autophagic apparatus. The end results, visualized by the group, were multimembranous structures that …