Prostate cancer cells metabolize d‐lactate inside mitochondria via a d‐lactate dehydrogenase which is more active and highly expressed than in normal cells

Although d-lactate metabolism has been shown to occur in a variety of mitochondria, the metabolic fate of d-lactate in cancer cells has never been investigated, as it is believed to be exported to the extracellular phase. We show that mitochondria from both cancer (PC-3) and normal (PNT1A) prostate cells can metabolize d-lactate in an energy competent manner. This is due to the mitochondrial d-lactate dehydrogenase, a membrane flavoprotein, the activity and protein level of which are higher in PC-3 than in PNT1A cells, as detected by both kinetic and immunological analysis. d-Lactate can enter prostate mitochondria and cause the export of newly synthesized malate in a carrier-mediated manner, with the rate of malate efflux from mitochondria twofold higher in cancer.