Unappreciated Role of LDHA and LDHB to Control Apoptosis and Autophagy in Tumor Cells

Abstract

Tumor cells possess a high metabolic plasticity, which drives them to switch on the anaerobic glycolysis and lactate production when challenged by hypoxia. Among the enzymes mediating this plasticity through bidirectional conversion of pyruvate and lactate, the lactate dehydrogenase A (LDHA) and lactate dehydrogenase B (LDHB), are indicated. LDHA has a higher affinity for pyruvate, preferentially converting pyruvate to lactate, and NADH to NAD ⁺ in anaerobic conditions, whereas LDHB possess a higher affinity for lactate, preferentially converting lactate to pyruvate, and NAD ⁺ to NADH, when oxygen is abundant. Apart from the undisputed role of LDHA and LDHB in tumor cell metabolism and adaptation to unfavorable environmental or cellular conditions, these enzymes participate in the regulation of cell death. This review presents the latest progress made in this area on the roles of LDHA and LDHB in apoptosis and autophagy of tumor cells. Several examples of how LDHA and LDHB impact on these processes, as well as possible molecular mechanisms, will be discussed in this article. The information included in this review points to the legitimacy of modulating LDHA and/or LDHB to target tumor cells in the context of human and veterinary medicine.