Apoptotic mitochondria blow a fuse

ranscription factor JunB negatively regulates proliferation in several cell types. But Kenner et al. (page 613) show that JunB, which acts as one-half of an AP-1 dimer, is a positive regulator of both osteo-blast and osteoclast proliferation and differentiation. In the process they have produced a new animal model for studying osteoporosis. As JunB is essential for placenta formation, the authors conditionally deleted the gene in embryonic tissues. The resulting mice were viable, but soon developed severe bone loss resembling human senile osteoporosis, and later a condition resembling chronic myelogenous leukemia. A separate strain of mice, lacking JunB only in the macrophage and osteoclast lineage, but not in osteoblasts, developed severe osteopetrosis and increased bone mass. The leukemia is consistent with earlier results suggesting a tumor–suppressor function for JunB, which negatively regulates the proliferation of myeloid progenitor cells. Osteoblast and osteoclast proliferation, however, seem to be boosted by JunB, and ex vivo experiments confirm that this effect is cell autonomous. Thus, JunB is a key regulator of bone growth and affects bone formation more strongly than resorption. ᭿ T Osteoclast differentiation fails in mice lacking JunB (right). Apoptotic mitochondria blow a fuse itochondrial networks fragment during apoptosis, and it is known that fission increases. Any fission increase is usually accompanied by a fusion increase, but on page 493 Karbowski et al. find that activating apoptosis blocks mitochondrial fusion. The authors came up with a clever new technique to track individual organelles using a photoactivatable form of GFP with a mitochondrial targeting sequence. Aiming a laser at individual mitochondria in tagged cells activated the fluorescent tag, and the dilution of fluorescence provided a quantitative readout of organelle fusion and fission. Inducing apoptosis blocked mitochondrial fusion to a degree that could fully account for apoptotic mitochondrial fragmentation. The block in fusion occurs around the same time as Bax translocation to mitochondria and mitochondrial permeabilization, and before caspase activation. The data suggest that a complete block in mitochondrial fusion is a normal part of apoptosis, and that this block is either fully or partially responsible for mitochondrial fragmentation. The authors are now adapting their assay to study mitochondrial fragmentation in more detail, and suggest that it could be used for high-resolution studies on the dynamics of other organelles. ᭿ M Local photoactivation (green) shows that mitochondrial fusion is inhibited by apoptosis onset. he yeast Saccharomyces cerevisae is a popular model for studying apoptosis, …