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Using an Extracellular Flux Analyzer to Measure Changes in Glycolysis and Oxidative Phosphorylation during Mouse Sperm Capacitation
Published on: January 22, 2020
Iron regulatory protein 2 modulates the switch from aerobic glycolysis to oxidative phosphorylation in mouse
Huihui Li1, Yutong Liu1, Longcheng Shang2
1Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, People's Republic of China.
Abstract:
The importance of the role of iron regulatory proteins (IRPs) in mitochondrial iron homeostasis and function has been raised. To understand how an IRP affects mitochondrial function, we used globally Irp2-depleted mouse embryonic fibroblasts (MEFs) and found that Irp2 ablation significantly induced the expression of both hypoxia-inducible factor subunits, Hif1α and Hif2α. The increase of Hif1α up-regulated its targeted genes, enhancing glycolysis, and the increase of Hif2α down-regulated the expression of iron-sulfur cluster (Fe-S) biogenesis-related and electron transport chain (ETC)-related genes, weakening mitochondrial respiration. Inhibition of Hif1α by genetic knockdown or a specific inhibitor prevented Hif1α-targeted gene expression, leading to decreased aerobic glycolysis. Inhibition of Hif2α by genetic knockdown or selective disruption of the heterodimerization of Hif2α and Hif1β restored the mitochondrial ETC and coupled oxidative phosphorylation (OXPHOS) by enhancing Fe-S biogenesis and increasing ETC-related gene expression. Our results indicate that Irp2 modulates the metabolic switch from aerobic glycolysis to OXPHOS that is mediated by Hif1α and Hif2α in MEFs.
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