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Mol Med Rep. 2018 Aug;18(2):1710-1717. doi: 10.3892/mmr.2018.9079. Epub 2018 May 29.

Hypoxia induces lactate secretion and glycolytic efflux by downregulating mitochondrial pyruvate carrier levels in human umbilical vein endothelial cells.

Author information

1
Department of Cardiology, Zhongda Hospital of Southeast University Medical School, Nanjing, Jiangsu 210009, P.R. China.
2
Department of Cardiology, Changzhou Hospital of Nanjing Medical University, Changzhou, Jiangsu 213004, P.R. China.

Abstract

The mitochondrial pyruvate carrier (MPC) complex, located on the inner mitochondrial membrane, transports pyruvate to the mitochondrial matrix for oxidative phosphorylation. Previous studies have shown that the MPC complex is a key regulator of glycolysis in tumor cells. The present study evaluated the role of the MPC under hypoxic conditions in human umbilical vein endothelial cells, which rely on glycolysis for energy generation. It was indicated that hypoxia led to an increase in lactate secretion and a decrease in MPC1 and MPC2 levels, which were upregulated following re‑oxygenation. In addition, the knockdown of MPC1 or treatment with the MPC inhibitor UK5099 increased the levels of glycolytic enzymes, HK2, PFKFB3, and LDHA, promoting glycolysis and lactate secretion. Taken together, the present data revealed that hypoxia can induce lactate secretion and glycolytic efflux by downregulating MPC levels.

PMID:
29845198
DOI:
10.3892/mmr.2018.9079

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