Mitochondrial caspase keeps autophagy in flux

M any cellular stresses, including starvation, induce cells to up-regulate the process of auto-phagy, in which cytoplasmic content is engulfed into autophagosomes and delivered to lysosomes for degradation. Auto-phagy can promote cell homeostasis and survival by removing damaged proteins and organelles and recycling their breakdown products to enhance cell metabolism. On the other hand, autophagy can contribute to cell death by digesting components of the dying cell. Both of these functions are important during development , and DeVorkin et al. describe how the caspase Dcp-1 promotes autophagy during Drosophila oogenesis (1). Drosophila egg chambers consist of an oocyte and a group of supportive nurse cells, surrounded by a layer of somatic follicle cells. Flies shut off egg production when nutrients are scarce, with midstage egg chambers undergoing cell death and degenera-tion (2). Autophagy is up-regulated in these egg chambers (3, 4), and in 2008 Sharon Gorski's lab at the Genome Sciences Centre in Vancouver, British Columbia, found that the death-promoting caspase Dcp-1 was required for this starvation-induced increase in autophagosome formation (4). " It was quite a surprise to fi nd that a classic apoptosis protein also controls autophagy, " Gor-ski says. " We wanted to explore the mechanism by which Dcp-1 does this. " Gorski and colleagues, led by graduate student Lindsay DeVorkin, fi rst ascertained that Dcp-1 regulates autophagic fl ux, or lysosome-mediated degradation of auto-phagosomes, in nutritionally starved egg chambers (1). In wild-type ovaries, auto-phagy occurred in both degenerating and nondegenerating egg chambers, indicating that it contributes to cell homeostasis as well as to starvation-induced cell death. But in starved egg chambers lacking Dcp-1, the number of autolysosomes—the product of autophagosome fusion with lysosomes— was greatly reduced, and a model auto-phagy substrate was not as effi ciently degraded , confi rming that the caspase promotes autophagic fl ux. To investigate how Dcp-1 might accomplish this, DeVorkin et al. examined the pro-tein's subcellular localization and found that the full-length, inactive form of the caspase (pro–Dcp-1) concentrated inside mitochon-dria. " In the absence of Dcp-1, we observed an increase in mitochondria with an elongated morphology in both nutrient-rich and starvation conditions, " Gorski explains. Dcp-1 therefore helps maintain the normal, shorter morphology of mitochondria in vivo. In wild-type egg chambers, mito-chondria only elongate in response to nutrient deprivation. " It was shown previously that mitochondrial elongation helps to sustain cellular ATP levels following starvation, " Gorski says. " That …