Lactate metabolism is associated with mammalian mitochondria.
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 both13C 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.
Department of Chemistry, Washington University, St. Louis, Missouri, USA.
Ying-Jr
YJ
Chen
Department of Chemistry, Washington University, St. Louis, Missouri, USA.
Nathaniel G
NG
Mahieu
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.|Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida, USA.
Xiaojing
X
Huang
Department of Chemistry, Washington University, St. Louis, Missouri, USA.
Manmilan
M
Singh
Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida, USA.
Peter A
PA
Crawford
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.
Stephen L
SL
Johnson
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Richard W
RW
Gross
Department of Chemistry, Washington University, St. Louis, Missouri, USA.
Jacob
J
Schaefer
Department of Chemistry, Washington University, St. Louis, Missouri, USA.|Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Gary J
GJ
Patti
D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D015394:Molecular Structure
D019344:Lactic Acid