title: Role of mitochondrial remodeling in programmed cell death in Drosophila melanogaster.
abstract: The role of mitochondria in Drosophila programmed cell death remains unclear, although certain gene products that regulate cell death seem to be evolutionarily conserved. We find that developmental programmed cell death stimuli in vivo and multiple apoptotic stimuli ex vivo induce dramatic mitochondrial fragmentation upstream of effector caspase activation, phosphatidylserine exposure, and nuclear condensation in Drosophila cells. Unlike genotoxic stress, a lipid cell death mediator induced an increase in mitochondrial contiguity prior to fragmentation of the mitochondria. Using genetic mutants and RNAi-mediated knockdown of drp-1, we find that Drp-1 not only regulates mitochondrial fission in normal cells, but mediates mitochondrial fragmentation during programmed cell death. Mitochondria in drp-1 mutants fail to fragment, resulting in hyperplasia of tissues in vivo and protection of cells from multiple apoptotic stimuli ex vivo. Thus, mitochondrial remodeling is capable of modifying the propensity of cells to undergo death in Drosophila.
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK-Campus, Bellary Road, Bangalore 560 065, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Goyal
authors.forename: Brennan
authors.initials: B
authors.lastname: Fell
authors.forename: Apurva
authors.initials: A
authors.lastname: Sarin
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Youle
authors.forename: V
authors.initials: V
authors.lastname: Sriram
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D053938:DNA Fragmentation; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; D020169:Caspases; C504426:DRP1 protein, Drosophila; D019204:GTP-Binding Proteins