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

Molecular Medicine Reports
Dong WangChengchun Tang

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.

References

Feb 1, 1995·The Journal of Clinical Investigation·A V Tretyakov, H W Farber
Jun 22, 2000·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·T Bachetti, L Morbidelli
May 4, 2004·Nature Reviews. Molecular Cell Biology·Christopher J Schofield, Peter J Ratcliffe
Sep 10, 2004·Molecular Biology of the Cell·Yang-ja LeeRichard J Youle
Aug 26, 2009·The International Journal of Biochemistry & Cell Biology·Petr Jezek, Lydie Plecitá-Hlavatá
May 26, 2012·Science·Sébastien HerzigJean-Claude Martinou
Nov 20, 2012·Annual Review of Physiology·Peter Dromparis, Evangelos D Michelakis
Mar 23, 2013·British Journal of Pharmacology·Loganathan Chitra, Rathanam Boopathy
Apr 13, 2013·Circulation Research·Matthew A KlugeJoseph A Vita
Aug 6, 2013·Cell·Katrien De BockPeter Carmeliet
Mar 29, 2014·The Journal of Biological Chemistry·Jessica N PattersonJamie W Joseph
Apr 5, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Yiming XuYuqing Huo
May 17, 2014·Frontiers in Physiology·Xiaoqiang TangDe-Pei Liu
Apr 26, 2015·Biochemical and Biophysical Research Communications·Lantao ZhaoJia Liu
Jan 31, 2016·Biochimica Et Biophysica Acta·Tom Bender, Jean-Claude Martinou
May 21, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Jes-Niels BoeckelStefanie Dimmeler
Dec 28, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kyle S McCommisBrian N Finck
Mar 4, 2017·The Journal of Cell Biology·Ajit S DivakaruniAnne N Murphy
Jun 24, 2017·The EMBO Journal·Brian W WongPeter Carmeliet

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Citations

Oct 4, 2020·Cancers·Rosa Maria PascaleFrancesco Feo
May 18, 2021·Frontiers in Immunology·Sally A ClaytonAndrew R Clark

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