miR-14 regulates autophagy during developmental cell death by targeting ip3-kinase 2

Charles Nelson1, Victor Ambros2, Eric H Baehrecke1

  • 1Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Molecular Cell
|October 14, 2014
PubMed

Insights

MicroRNA miR-14 is essential for programmed cell death-related autophagy in Drosophila salivary glands. It regulates this process by targeting inositol 1,4,5-trisphosphate kinase 2, impacting calcium signaling.

Area of Science:

  • Cellular Biology
  • Developmental Biology
  • Molecular Genetics

Background:

  • Macroautophagy (autophagy) is a crucial lysosome-dependent degradation pathway implicated in age-associated diseases.
  • Autophagy plays a dual role in cell survival and cell death, yet the regulatory mechanisms distinguishing these fates remain unclear.

Purpose of the Study:

  • To investigate the role of microRNAs in regulating context-specific autophagy during development.
  • To identify the molecular mechanisms by which microRNAs control autophagy during programmed cell death.

Main Methods:

  • Utilized Drosophila melanogaster as an in vivo model system.
  • Employing genetic manipulation to assess the necessity and sufficiency of miR-14 in autophagy induction.
  • Investigated the downstream targets and signaling pathways affected by miR-14, including inositol 1,4,5-trisphosphate kinase 2 (ip3k2) and calcium signaling.

Main Results:

  • miR-14 was identified as both necessary and sufficient for inducing autophagy during developmentally regulated salivary gland cell death in Drosophila.
  • Loss of miR-14 specifically blocked autophagy in dying salivary glands but did not affect starvation-induced autophagy in the fat body.
  • Misexpression of miR-14 prematurely induced autophagy in salivary glands, confirming its context-specific role.
  • miR-14 regulates autophagy via its target ip3k2, modulating inositol 1,4,5-trisphosphate (IP3) signaling and intracellular calcium levels.

Conclusions:

  • This study provides the first in vivo evidence for microRNA-mediated regulation of autophagy.
  • miR-14 acts as a critical regulator of autophagy during programmed cell death in a tissue-specific manner.
  • The findings highlight a novel mechanism linking microRNA, IP3 signaling, and calcium homeostasis to autophagy control.

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