Including the mitochondrial metabolism of L-lactate in cancer metabolic reprogramming.

Abstract

Glucose avidity, high glycolysis and L-lactate production, regardless of oxygen availability, are the main traits of cancer metabolic reprogramming. The idea that mitochondria are dysfunctional in cancer, thus causing a glycolysis increase for ATP production and L-lactate accumulation as a dead-end product of glucose catabolism, has oriented cancer research for many years. However, it was shown that mitochondrial metabolism is essential for cancer cell proliferation and tumorigenesis and that L-lactate is a fundamental energy substrate with tumor growth-promoting and signaling capabilities. Nevertheless, the known ability of mitochondria to take up and oxidize L-lactate has remained ignored by cancer research. Beginning with a brief overview of the metabolic changes occurring in cancer, we review the present knowledge of L-lactate formation, transport, and intracellular oxidation and underline the possible role of L-lactate metabolism as energetic, signaling and anabolic support for cancer cell proliferation. These unexplored aspects of cancer biochemistry might be exploited for therapeutic benefit.