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Updated: Aug 8, 2025

An Optimized Protocol to Analyze Glycolysis and Mitochondrial Respiration in Lymphocytes
Published on: November 21, 2016
Nitration-mediated activation of the small GTPase RhoA stimulates cellular glycolysis through enhanced mitochondrial
Qing Lu1, Xutong Sun1, Manivannan Yegambaram2
1Center of Translational Science, Florida International University, Port St Lucie, Florida, USA; Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, Florida, USA.
Abstract:
Mitochondrial fission and a Warburg phenotype of increased cellular glycolysis are involved in the pathogenesis of pulmonary hypertension (PH). The purpose of this study was to determine whether increases in mitochondrial fission are involved in a glycolytic switch in pulmonary arterial endothelial cells (PAECs). Mitochondrial fission is increased in PAEC isolated from a sheep model of PH induced by pulmonary overcirculation (Shunt PAEC). In Shunt PAEC we identified increases in the S616 phosphorylation responsible for dynamin-related protein 1 (Drp1) activation, the mitochondrial redistribution of Drp1, and increased cellular glycolysis. Reducing mitochondrial fission attenuated cellular glycolysis in Shunt PAEC. In addition, we observed nitration-mediated activation of the small GTPase RhoA in Shunt PAEC, and utilizing a nitration-shielding peptide, NipR1 attenuated RhoA nitration and reversed the Warburg phenotype. Thus, our data identify a novel link between RhoA, mitochondrial fission, and cellular glycolysis and suggest that targeting RhoA nitration could have therapeutic benefits for treating PH.
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