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Nat Chem Biol. 2016 Nov;12(11):937-943. doi: 10.1038/nchembio.2172. Epub 2016 Sep 12.

Lactate metabolism is associated with mammalian mitochondria.

Author information

1
Department of Chemistry, Washington University, St. Louis, Missouri, USA.
2
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.
3
Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida, USA.
4
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Abstract

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.

PMID:
27618187
PMCID:
PMC5069139
DOI:
10.1038/nchembio.2172
[Indexed for MEDLINE]
Free PMC Article

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