Lactate Metabolism is Associated with Mammalian Mitochondria

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2016 Sep 13

PMID 27618187

Citations 147

Authors

Ying-Jr Chen

Nathaniel G Mahieu

Xiaojing Huang

Manmilan Singh

Peter A Crawford

Stephen L Johnson

Richard W Gross

Jacob Schaefer

Gary J Patti

Affiliations

Soon will be listed here.

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 C and 2-H 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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