| Cell death is an important process during development and disease; the Drosophila ovary provides an excellent model for investigating this vital process. Late in oogenesis, ovarian nurse cells transfer their cytoplasmic contents to the developing oocyte, and then the remains of the nurse cells are removed through unknown mechanisms.;Cell death also occurs during mid-oogenesis in response to nutrient deprivation. During cell death in mid-oogenesis, entire follicles are removed. Cell deaths in mid and late oogenesis occur by pathways that are distinct from each other and from pathways controlling most other Drosophila cell deaths. The Bcl-2 family has been shown to regulate mitochondrial dynamics during cell death in other organisms, but evidence for this in Drosophila has been elusive. Here, regulation of mitochondria dynamics during germline cell death in the Drosophila melanogaster ovary is investigated.;In mid-oogenesis, cell death occurs through an atypical caspase cascade with an unknown activation mechanism. Mitochondria were found to undergo a series of events during the progression of cell death, with remodeling, cluster formation and uptake of clusters by somatic follicle cells. These mitochondrial dynamics were dependent on caspases, the Bcl-2 family, the mitochondrial fission and fusion machinery, and the autophagy machinery. Furthermore, Bcl-2 family mutants showed a striking defect in cell death in the ovary. These data indicate that a mitochondrial pathway is a major mechanism for activation of cell death in mid-oogenesis.;Developmental cell death is even more unusual than mid-oogenesis cell death in that it is only partially caspase dependent. The Bcl-2 family and mitochondrial fission and fusion mutants were found to recapitulate the caspase inhibition phenotype. Interestingly, analysis of mitochondrial dynamics and other organelle changes showed hallmarks of programmed necrosis including mitochondrial clustering and lysosomal rupture. These findings demonstrate that mitochondria play important roles during cell death in the Drosopila ovary. |
