MicroRNA-137 is a Novel Hypoxia-responsive MicroRNA That Inhibits Mitophagy Via Regulation of Two Mitophagy Receptors FUNDC1 and NIX

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2014 Feb 28

PMID 24573672

Citations 70

Authors

Wen Li

Xingli Zhang

Haixia Zhuang

He-Ge Chen

Yinqin Chen

Weili Tian

Wenxian Wu

Ying Li

Sijie Wang

Liangqing Zhang

Yusen Chen

Longxuan Li

Bin Zhao

SenFang Sui

Zhe Hu

Du Feng

Affiliations

Soon will be listed here.

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.

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