Journal
NATURE CHEMICAL BIOLOGY
Volume 12, Issue 11, Pages 937-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.2172
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Funding
- National Institutes of Health [R01 ES022181, R21 CA191097-01A1, R01 HL118639-03, R01 DK091538, R01 EB002058]
- Alfred P. Sloan Foundation
- Camille & Henry Dreyfus Foundation
- Pew Scholars Program in the Biomedical Sciences
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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 C-13 and 2-H-2 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.
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