Lactate metabolism is associated with mammalian mitochondria

Ying Jr Chen, Nathaniel G. Mahieu, Xiaojing Huang, Manmilan Singh, Peter A. Crawford, Stephen L. Johnson, Richard W. Gross, Jacob Schaefer, Gary J. Patti

Research output: Contribution to journalArticlepeer-review

167 Scopus citations


It is well established that lactate secreted by fermenting cells can be oxidized or used as a gluconeogenic substrate by other cells and tissues. It is generally assumed, however, that within the fermenting cell itself, lactate is produced to replenish NAD+ and then is secreted. Here we explore the possibility that cytosolic lactate is metabolized by the mitochondria of fermenting mammalian cells. We found that fermenting HeLa and H460 cells utilize exogenous lactate carbon to synthesize a large percentage of their lipids. Using high-resolution mass spectrometry, we found that both 13C and 2-2H labels from enriched lactate enter the mitochondria. The lactate dehydrogenase (LDH) inhibitor oxamate decreased respiration of isolated mitochondria incubated in lactate, but not of isolated mitochondria incubated in pyruvate. Additionally, transmission electron microscopy (TEM) showed that LDHB localizes to the mitochondria. Taken together, our results demonstrate a link between lactate metabolism and the mitochondria of fermenting mammalian cells.

Original languageEnglish (US)
Pages (from-to)937-943
Number of pages7
JournalNature Chemical Biology
Issue number11
StatePublished - Nov 1 2016

Bibliographical note

Funding Information:
This work was supported by funding from the National Institutes of Health grants R01 ES022181 (G.J.P.), R21 CA191097-01A1 (G.J.P.), R01 HL118639-03 (R.W.G.), R01 DK091538 (P.A.C.), and R01 EB002058 (J.S.), as well as grants from the Alfred P. Sloan Foundation (G.J.P.), the Camille & Henry Dreyfus Foundation (G.J.P.), and the Pew Scholars Program in the Biomedical Sciences (G.J.P.). We thank W. Beatty at Washington University's Molecular Microbiology Imaging Facility for acquiring the TEM images.

Publisher Copyright:
© 2016 Nature America, Inc. All rights reserved.


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