Inhibition of Hif1α in Irp2−/− cells suppressed the Hif1α target genes HK2, Glut1, and LdhA. As a result, aerobic glycolysis was repressed, and the lactic acid levels decreased, whereas OXPHOS-related genes and enzyme activities did not respond to Hif1α inhibition.

Our results indicate that Irp2 depletion-induced Hif2α is, in vivo, in charge of the switch between OXPHOS and glycolysis, suggesting that, for the first time to our knowledge, Hif2α is a clinically potential target in the treatment of IRP2 deficiency-induced neurodegenerative syndrome.

Aug 19, 2020 · Elevated Hif1α enhances glycolysis by targeting a number of glycolytic pathway-related genes, including hexokinase 2 (Hk2), glucose transporter type 1 (Glut1) and lactate dehydrogenase A/B (LdhA/B).

. IRP2 deficiency causes energy metabolic reprogramming by inducing the expressions of Hif1 α and Hif2 in cance cells. The IRP2-Hif1 /Hif2 pathway plays an α α α important role in fumarate hydratase (FH)-deficient kidney tumors. The inactivation of TCA cycle enzymes drives a …

Our results indicate that Irp2 modulates the metabolic switch from aerobic glycolysis to OXPHOS that is mediated by Hif1 and Hif2 in MEFs. biochemical pathways, including hemoglobin synthesis and the mitochondrial respiration chain.

Two cytoplasmic proteins with mRNA-binding properties, iron regulatory proteins 1 and 2 (IRP1 and IRP2) play a central role in this regulation. Foremost, IRPs regulate ferritin H and ferritin L translation and thus iron storage, as well as transferrin receptor 1 (TfR1) mRNA stability, thereby adjusting receptor expression and iron uptake via ...

Oct 5, 2022 · At the cellular level, iron homeostasis is orchestrated by the interaction of iron regulatory protein 1 (IRP1) and IRP2 (also known as ACO1 and IREB2, respectively) with cis-regulatory iron responsive elements (IREs) present in the untranslated region (UTR) of mRNAs encoding iron metabolism molecules.

Apr 30, 2019 · Irp2 knockout mice show symptoms of neurological disorders, which are considered to result from impaired mitochondrial activity. To explore the involvement of Irp2 in mitochondrial function, we...

Our previous in vitro data have demonstrated that Irp2 depletion upregulates hypoxia-inducible factor subunits Hif1α and Hif2α expression; inhibition of Hif2α rescues Irp2 ablation-induced ...

Apr 30, 2019 · Inhibition of Hif1α in Irp2−/− cells suppressed the Hif1α target genes HK2, Glut1, and LdhA. As a result, aerobic glycolysis was repressed, and the lactic acid levels decreased, whereas OXPHOS-related genes and enzyme activities did not respond to Hif1α inhibition.