miR-14 Regulates Autophagy during Developmental Cell Death by Targeting ip3-kinase 2
Open accessAbstract
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.
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Developmental degradation of Drosophila salivary glands by autophagy requires Utx, miR-14, Rala, Drpr, and Mcr.
“Moreover, the developmental degradation of Drosophila salivary glands by autophagy requires the activity of: (1) Utx histone demethylase (Utx), which contributes to the transcriptional regulation of apoptosis and autophagy genes [839]; (2) miR-14, which specifically activates autophagy-dependent cell death by modulating multiple IP3-driven signaling pathways upon targeting inositol 1,4,5-triphosph”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [840]
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- Authors
- Nelson, C., Ambros, V., & Baehrecke, E. H.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Baehrecke, Eric H.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 56
- Issue
- 3
- Pages
- 376-388
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1969567490
- Cited by
- 61
- References
- 34
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 8 · 2016: 4 · 2015: 11 · 2014: 1
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- National Institutes of Health (GM079431-04S1, R01GM34028)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- autophagy, developmental cell death, IP3 signaling, calcium signaling, fat body, Drosophila
- MeSH terms
- Animals, Autophagy, Calcium, Cell Line, Drosophila melanogaster, Larva, Salivary Glands, Second Messenger Systems, Inositol 1,4,5-Trisphosphate, Phosphotransferases (Alcohol Group Acceptor), Drosophila Proteins, RNA Interference, MicroRNAs
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