title: Mutants forDrosophilaIsocitrate Dehydrogenase 3b Are Defective in Mitochondrial Function and Larval Cell Death.
abstract: The death of larval salivary gland cells during metamorphosis inDrosophila melanogasterhas been a key system for studying steroid controlled programmed cell death. This death is induced by a pulse of the steroid hormone ecdysone that takes place at the end of the prepupal period. For many years, it has been thought that the ecdysone direct response geneEip93F(E93) plays a critical role in initiating salivary gland cell death. This conclusion was based largely on the finding that the three "type" alleles ofE93cause a near-complete block in salivary gland cell death. Here, we show that these three mutations are in fact allelic toIdh3b, a nearby gene that encodes the β subunit of isocitrate dehydrogenase 3, a mitochondrial enzyme of the tricarboxylic acid (TCA) cycle. The strongest of theIdh3balleles appears to cause a near-complete block in oxidative phosphorylation, as mitochondria are depolarized in mutant larvae, and development arrests early during cleavage in embryos from homozygous-mutant germline mothers.Idh3b-mutant larval salivary gland cells fail to undergo mitochondrial fragmentation, which normally precedes the death of these cells, and do not initiate autophagy, an early step in the cell death program. These observations suggest a close relationship between the TCA cycle and the initiation of larval cell death. In normal development, tagged Idh3b is released from salivary gland mitochondria during their fragmentation, suggesting that Idh3b may be an apoptogenic factor that functions much like released cytochromecin mammalian cells.
authors.affiliation: Department of Biology, Washington University, St. Louis, Missouri 63130.
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Duncan
authors.affiliation: Department of Biology, Washington University, St. Louis, Missouri 63130.
authors.forename: Paula
authors.initials: P
authors.lastname: Kiefel
authors.affiliation: Department of Biology, Washington University, St. Louis, Missouri 63130 duncan@wustl.edu.
authors.forename: Ian
authors.initials: I
authors.lastname: Duncan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000483:Alleles; D000818:Animals; D001343:Autophagy / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002874:Chromosome Mapping; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism; D019076:Transgenes
chemical_list: D029721:Drosophila Proteins; D000255:Adenosine Triphosphate; C000627648:Idh3b protein, Drosophila; D007521:Isocitrate Dehydrogenase
keywords: E93; Idh3b; apoptosis; autophagy; isocitrate dehydrogenase; mitochondria