Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression.
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.
Chen
Z
Z
Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Li
Y
Y
Zhang
H
H
Huang
P
P
Luthra
R
R
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
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