Metabolic Transporters in the Peripheral Nerve-What, Where, and Why?

Cellular metabolism is critical not only for cell survival, but also for cell fate, function, and intercellular communication. There are several different metabolic transporters expressed in the peripheral nervous system, and they each play important roles in maintaining cellular energy. The major source of energy in the peripheral nervous system is glucose, and glucose transporters 1 and 3 are expressed and allow blood glucose to be imported and utilized by peripheral nerves. There is also increasing evidence that other sources of energy, particularly monocarboxylates such as lactate that are transported primarily by monocarboxylate transporters 1 and 2 in peripheral nerves, can be efficiently utilized by peripheral nerves. Finally, emerging evidence supports an important role for connexins and possibly pannexins in the supply and regulation of metabolic energy. In this review, we will first define these critical metabolic transporter subtypes and then examine their localization in the peripheral nervous system. We will subsequently discuss the evidence, which comes both from experiments in animal models and observations from human diseases, supporting critical roles played by these metabolic transporters in the peripheral nervous system. Despite progress made in understanding the function of these transporters, many questions and some discrepancies remain, and these will also be addressed throughout this review. Peripheral nerve metabolism is fundamentally important and renewed interest in these pathways should help to answer many of these questions and potentially provide new treatments for neurologic diseases that are partly, or completely, caused by disruption of metabolism.