Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 289, Issue 15, Pages 10691-10701Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.537050
Keywords
Autophagy; Hypoxia; MicroRNA; Mitochondria; Parkin; FUNDC1; Mitophagy; NIX
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Funding
- Guangdong Medical College [B2012043, B2012044, 701B01206]
- National Natural Science Foundation of China [81171244, 31301104]
- Guangdong Natural Science Foundation of China [S2011010004095]
- Ministry of Education for returning-back scholars of China [[2012]940]
- Foundation for Distinguished Young Talents in Higher Education of Guangdong, China [2013LYM_0035]
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Background: Mitophagy and microRNA both regulate the occurrence of neurodegenerative diseases and cancers. Results: MicroRNA-137, a hypoxia responsive microRNA, inhibits mitophagy via targeting two mitophagy receptors. Conclusion: A novel link between miR-137 and mitophagy has been revealed. Significance: Understanding mitophagy regulation and microRNA functions may provide new concepts to fight human diseases. 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+3UTR) 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.
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