Death-defying tactics

Death-defying tact ics T here may be 101 ways to kill a cell, but for each there is an escape route. Cells that escape apoptosis, report Anna Colell (Institut d’Investigacions Biomediques de Barcelona, Spain), Jean-Ehrland Ricci (Université de Nice Sophia-Antipolis, France), Douglas Green (St Jude’s Children’s Research Hospital, Memphis, TN), and colleagues, also have a way to escape the back-up killing mechanism that kicks in. An early step in apoptosis is the permeabilization of mitochondrial membranes. Mitochondria then lose cytochrome C, which triggers caspase activation and death. For cells that manage to inhibit caspases, there is always plan B—caspaseindependent cell death (CICD). An escape from CICD has been reported for starving neurons, but it’s also possible that defeating CICD might be one way to transform cancer cells. Colell et al. screened a cDNA library for genes that protected cells from CICD. They found GAPDH. High levels of this enzyme led to increases in glycolysis and ATP levels and also to autophagy. The team showed that GAPDH increased the expression of an autophagy-promoting gene. Both glycolysis and autophagy were necessary for protection from CICD. Evidence also suggests that autophagosomes might be gobbling up the defective mitochondria. Thus the rise in GAPDH might provide energy for both mitochondrial repair and clearing up damaged mitochondrial remains. Reference: Colell, A., et al. 2007. Cell. 129:983–997. Golgi lands new role W hen it comes to microtubule organization, centrosomes have the lead role. But, as Andrey Efi mov, Irina Kaverina (Vanderbilt University Medical Center, Nashville, TN), Alexey Kharitonov (Austrian Academy of Sciences, Vienna, Austria), and colleagues now report, the Golgi shares some of the limelight. Unlike centrosomes, this new-found organizer doesn’t symmetrically radiate microtubules from center stage, but instead directs its performance to one cell edge. Microtubules do not start growing spontaneously in cells; they rely on supporting protein machinery to nucleate tubulin building blocks and kick off polymerization. To fi nd their origins, Efi mov et al. tracked the growth of new microtubules in living cells. They found that the majority of new microtubules radiated out from a central position in the cell that is consistent with centrosomes. A signifi cant proportion of nucleation events, however, appeared to occur at the Golgi. When the team obliterated centrosomes using laser beams, they found that new microtubules indeed continued to sprout from the Golgi. Golgi, but not centrosomal, nucleation required a microtubule-binding protein called CLASP. Microtubules grew out from Golgi in one direction—away from the nucleus and toward the cell’s periphery. In migrating cells, this directionality corresponded with the direction of migration, as microtubules from the Golgi grew toward the cell’s leading edge. Golgi-mediated nucleation might therefore support the asymmetric architecture and secretory vesicle traffi cking of polarized motile cells.