title: MicroRNA-137 is a novel hypoxia-responsive microRNA that inhibits mitophagy via regulation of two mitophagy receptors FUNDC1 and NIX.
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.
authors.affiliation: Institute of Neurology, Guangdong Key Laboratory of Age-related Cardiac-cerebral Vascular Disease, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Neurology, Guangdong Key Laboratory of Age-related Cardiac-cerebral Vascular Disease, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong.
authors.forename: Xingli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong.
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Department of Urology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong.
authors.forename: He-Ge
authors.initials: HG
authors.lastname: Chen
authors.affiliation: Department of Interventional Radiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong.
authors.forename: Yinqin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Neurology, Guangdong Key Laboratory of Age-related Cardiac-cerebral Vascular Disease, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong.
authors.forename: Weili
authors.initials: W
authors.lastname: Tian
authors.affiliation: Institute of Neurology, Guangdong Key Laboratory of Age-related Cardiac-cerebral Vascular Disease, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong.
authors.forename: Wenxian
authors.initials: W
authors.lastname: Wu
authors.affiliation: Cell Biology Core Facility, Center for Biomedical Analysis, Tsinghua University, Beijing 100084.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Clinic Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong.
authors.forename: Sijie
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong.
authors.forename: Liangqing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Neurology, Guangdong Key Laboratory of Age-related Cardiac-cerebral Vascular Disease, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong.
authors.forename: Yusen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Neurology, Guangdong Key Laboratory of Age-related Cardiac-cerebral Vascular Disease, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong; Department of Neurology, Gongli Hospital, Pudong New Area, Shanghai 200135.
authors.forename: Longxuan
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Neurology, Guangdong Key Laboratory of Age-related Cardiac-cerebral Vascular Disease, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Senfang
authors.initials: S
authors.lastname: Sui
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong. Electronic address: biohuzhe@hotmail.com.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Institute of Neurology, Guangdong Key Laboratory of Age-related Cardiac-cerebral Vascular Disease, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong. Electronic address: feng_du@foxmail.com.
authors.forename: Du
authors.initials: D
authors.lastname: Feng
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001343:Autophagy; D015687:Cell Hypoxia; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C000588786:FUNDC1 protein, mouse; C551799:MIRN137 microRNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D024101:Mitochondrial Proteins; C501741:Nix protein, mouse
keywords: Autophagy; FUNDC1; Hypoxia; MicroRNA; Mitochondria; Mitophagy; NIX; Parkin