title: miR-14 regulates autophagy during developmental cell death by targeting ip3-kinase 2.
abstract: Macroautophagy (autophagy) is a lysosome-dependent degradation process that has been implicated in age-associated diseases. Autophagy is involved in both cell survival and cell death, but little is known about the mechanisms that distinguish its use during these distinct cell fates. Here, we identify the microRNA miR-14 as being both necessary and sufficient for autophagy during developmentally regulated cell death in Drosophila. Loss of miR-14 prevented induction of autophagy during salivary gland cell death, but had no effect on starvation-induced autophagy in the fat body. Moreover, misexpression of miR-14 was sufficient to prematurely induce autophagy in salivary glands, but not in the fat body. Importantly, miR-14 regulates this context-specific autophagy through its target, inositol 1,4,5-trisphosphate kinase 2 (ip3k2), thereby affecting inositol 1,4,5-trisphosphate (IP3) signaling and calcium levels during salivary gland cell death. This study provides in vivo evidence of microRNA regulation of autophagy through modulation of IP3 signaling.
authors.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Nelson
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Ambros
authors.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: eric.baehrecke@umassmed.edu.
authors.forename: Eric H
authors.initials: EH
authors.lastname: Baehrecke
mesh_terms: D000818:Animals; D001343:Autophagy; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology / Q000254:growth & development; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D035683:MicroRNAs / Q000502:physiology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012469:Salivary Glands / Q000166:cytology; D015290:Second Messenger Systems
chemical_list: D029721:Drosophila Proteins; C555944:MIRN14 microRNA, Drosophila; D035683:MicroRNAs; D015544:Inositol 1,4,5-Trisphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C000595571:inositol 1,4,5-trisphosphate kinase 2, Drosophila; D002118:Calcium