Mitochondrial fission regulates the development of Drosophila egg chambers, Mitra et al. reveal.
Fusion and fission proteins shape mitochondria into either long, interconnected tubules or shorter fragments dispersed throughout the cytoplasm. Mitra et al. previously found that tissue culture cells must fuse their mitochondria into a large network in order to enter S phase and progress through the cell cycle. To determine whether mitochondrial morphology has a similar function in vivo, the researchers investigated how follicle cells—the outer layer of Drosophila egg chambers—develop in the absence of the mitochondrial fission protein DRP1.
Most follicle cells proliferate until the Notch signaling pathway induces cell cycle exit and differentiation into a polarized epithelium. In the absence of DRP1, however, the follicle cells nearest to the oocyte maintained a highly fused mitochondrial network and continued to proliferate instead of differentiating. The Notch receptor wasn't activated in DRP1-null cells, but Notch signaling and differentiation were restored if the mitochondrial network was dispersed by simultaneously depleting the mitochondrial fusion protein Marf-1.
When Marf-1 alone was depleted—leaving the fission activity of DRP1 unopposed—follicle cells differentiated prematurely, at a stage when they should have continued to proliferate. This suggests that DRP1-dependent mitochondrial fission initiates follicle cell differentiation, perhaps because cells’ energetic requirements change when they stop proliferating, necessitating a change in mitochondrial morphology. The authors, from Jennifer Lippincott-Schwartz's lab, now want to investigate whether mitochondrial organization also regulates the differentiation of pluripotent stem cells and to determine whether cancer cells are affected by changes in the organelle's morphology.
