title: Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression.
abstract: The mechanisms of compromised mitochondrial function under various pathological conditions, including hypoxia, remain largely unknown. Recent studies have shown that microRNA-210 (miR-210) is induced by hypoxia under the regulation of hypoxia-inducible factor-1alpha and has an important role in cell survival under hypoxic microenvironment. Hence, we hypothesized that miR-210 has a role in regulating mitochondrial metabolism and investigated miR-210 effects on mitochondrial function in cancer cell lines under normal and hypoxic conditions. Our results demonstrate that miR-210 decreases mitochondrial function and upregulates the glycolysis, thus make cancer cells more sensitive to glycolysis inhibitor. miR-210 can also activate the generation of reactive oxygen species (ROS). ISCU (iron-sulfur cluster scaffold homolog) and COX10 (cytochrome c oxidase assembly protein), two important factors of the mitochondria electron transport chain and the tricarboxylic acid cycle have been identified as potential targets of miR-210. The unique means by which miR-210 regulates mitochondrial function reveals an miRNA-mediated link between microenvironmental stress, oxidative phosphorylation, ROS and iron homeostasis.
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: P
authors.initials: P
authors.lastname: Huang
authors.forename: R
authors.initials: R
authors.lastname: Luthra
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003576:Electron Transport Complex IV; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000235:genetics*; D035683:MicroRNAs / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D010101:Oxygen Consumption; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C506160:ISCU protein, human; D007506:Iron-Sulfur Proteins; C543800:MIRN210 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D017382:Reactive Oxygen Species; C490115:COX10 protein, human; D003576:Electron Transport Complex IV; D019883:Alkyl and Aryl Transferases