miR-14 Regulates Autophagy during Developmental Cell Death by Targeting ip3-kinase 2
Department of Cancer Biology; Program in Molecular Medicine
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Genomics | Molecular Biology | Molecular Genetics
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.
DOI of Published Version
Mol Cell. 2014 Nov 6;56(3):376-88. doi: 10.1016/j.molcel.2014.09.011. Epub 2014 Oct 9. Link to article on publisher's site
Nelson, Charles; Ambros, Victor R.; and Baehrecke, Eric H., "miR-14 Regulates Autophagy during Developmental Cell Death by Targeting ip3-kinase 2" (2014). Program in Molecular Medicine Publications and Presentations. 17.