Correction: Suppression of Mitochondrial Electron Transport Chain Function in the Hypoxic Human Placenta: A Role for miRNA-210 and Protein Synthesis Inhibition

Fetal growth is critically dependent on energy metabolism in the placenta, which drives active exchange of nutrients. Placental oxygen levels are therefore vital, and chronic hypoxia during pregnancy impairs fetal growth. Here we tested the hypothesis that placental hypoxia alters mitochondrial electron transport chain (ETS) function, and sought to identify underlying mechanisms. We cultured human placental cells under different oxygen concentrations. Mitochondrial respiration was measured, alongside levels of ETS complexes. Additionally, we studied placentas from sea-level and highaltitude pregnancies. After 4 d at 1% O2 (1.01 KPa), complex I-supported respiration was 57% and 37% lower, in trophoblast-like JEG3 cells and fibroblasts, respectively, compared with controls cultured at 21% O2 (21.24 KPa); complex IVsupported respiration was 22% and 30% lower. Correspondingly, complex I levels were 45% lower in placentas from highaltitude pregnancies than those from sea-level pregnancies. Expression of HIF-responsive microRNA-210 was increased in hypoxic fibroblasts and high-altitude placentas, whilst expression of its targets, iron-sulfur cluster scaffold (ISCU) and cytochrome c oxidase assembly protein (COX10), decreased. Moreover, protein synthesis inhibition, a feature of the highaltitude placenta, also suppressed ETS complex protein levels. Our results demonstrate that mitochondrial function is altered in hypoxic human placentas, with specific suppression of complexes I and IV compromising energy metabolism and potentially contributing to impaired fetal growth. Citation: Colleoni F, Padmanabhan N, Yung H-w, Watson ED, Cetin I, et al. (2013) Suppression of Mitochondrial Electron Transport Chain Function in the Hypoxic Human Placenta: A Role for Mirna-210 and Protein Synthesis Inhibition. PLoS ONE 8(1): e55194. doi:10.1371/journal.pone.0055194 Editor: Yidong Bai, University of Texas Health Science Center at San Antonio, United States of America Received August 2, 2012; Accepted December 19, 2012; Published January 30, 2013 Copyright: 2013 Colleoni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Dr Murray thanks the Research Councils UK for supporting his academic fellowship and Prof Burton gratefully acknowledges support for his research from the Wellcome Trust (084804/2/08/Z). This study was primarily supported by Action Medical Research, project grant number SP4545. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected] . These authors contributed equally to this work.