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MicroRNA-137 Is a Novel Hypoxia-responsive MicroRNA That Inhibits Mitophagy via Regulation of Two Mitophagy Receptors FUNDC1 and NIX
- Source :
- Journal of Biological Chemistry. 289:10691-10701
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Mitophagy receptors mediate the selective recognition and targeting of damaged mitochondria by autophagosomes. The mechanism for the regulation of these receptors remains unknown. Here, we demonstrated that a novel hypoxia-responsive microRNA, microRNA-137 (miR-137), markedly inhibits mitochondrial degradation by autophagy without affecting global autophagy. miR-137 targets the expression of two mitophagy receptors NIX and FUNDC1. Impaired mitophagy in response to hypoxia caused by miR-137 is reversed by re-expression of FUNDC1 and NIX expression vectors lacking the miR-137 recognition sites at their 3' UTR. Conversely, miR-137 also suppresses the mitophagy induced by fundc1 (CDS+3'UTR) but not fundc1 (CDS) overexpression. Finally, we found that miR-137 inhibits mitophagy by reducing the expression of the mitophagy receptor thereby leads to inadequate interaction between mitophagy receptor and LC3. Our results demonstrated the regulatory role of miRNA to mitophagy receptors and revealed a novel link between miR-137 and mitophagy.
- Subjects :
- Genetic Vectors
Biology
Mitochondrion
Biochemistry
Parkin
Mitochondrial Proteins
Mice
Phagosomes
microRNA
Mitophagy
Autophagy
Animals
Humans
Receptor
3' Untranslated Regions
Molecular Biology
Regulation of gene expression
HEK 293 cells
Membrane Proteins
Cell Biology
Fibroblasts
Cell Hypoxia
Mitochondria
Cell biology
Mice, Inbred C57BL
MicroRNAs
HEK293 Cells
Gene Expression Regulation
RNA
HeLa Cells
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 289
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....af074d8c72a73693f3c4ac04b2c87905