Ying-Jr Chen, Nathaniel G Mahieu, Xiaojing Huang, Manmilan Singh, Peter A Crawford, Stephen L Johnson, Richard W Gross, Jacob Schaefer, Gary J Patti
Lactate is sometimes referred to as "metabolic waste" but this has been established as a misnomer for quite some time, with it being shown as early as the 1920s that lactate can be transformed back into glucose via gluconeogenesis in the liver. There are multiple other examples where shuttling of lactate between tissues allows it to be metabolised. However, it remains controversial whether individual cells are able to metabolise this apparent metabolic by-product.
Here, the authors show that lactate is able to enter mitochondria and participate in mitochondrial energy metabolism. By culturing cells in radiolabelled lactate, the authors show that carbon from lactate can be found in intermediate metabolites of the TCA. They show that mitochondria are able to metabolize lactate, suggesting that they are able to import the metabolite, and that mitochondria possess the necessary enzyme (lactate dehydrogenase B) to convert lactate into the better-known mitochondrial substrate, pyruvate. The authors suggest this may be particularly relevant in cancer cells, which have particularly high glycolysis and lactate production.
Thoughts: It seems like a pretty important follow-up question to ask how much lactate is used by mitochondria relative to secretion in vivo. If the effect is big, doesn't this mean extracellular acidification rate is not a good metric of glycolysis levels?