Rethinking the regulation of L-carnitine transport in skeletal muscle cells. Focus on 'Multiple AMPK activators inhibit L-carnitine uptake in C2C12 skeletal muscle myotubes'

摘要

carnitine is a critical cofactor in the metabolism of lipids and therefore in the production of cellular energy. L-Carnitine, the active form, plays an important role in oxidizing fatty acids, transporting long chain fatty acids across mitochondrial membrane, and modulating intracellular coenzyme A homeostasis (3). L-Carnitine uptake into cells is mediated primarily by the organic cation/carnitine transporters (OCTN), a subclass of the solute carrier 22 transporter family. Patients bearing mutations in 0CTN2 gene exhibit severe symptoms because of the resulting cardiomyopathy, progressive skeletal weakness, non-ketotic hypoglycemia, and hyperammonemia (10). Currently the information on the regulation of L-carnitine transport into skeletal muscle cells is sparse. AMP-activated protein kinase (AMPK), a cellular energy sensor, usually acts to inhibit energy-utilizing pathways (e.g., fatty acid and protein synthesis) while boosting energy-generating pathways (e.g., glucose uptake and fatty acid oxidation) (2). Like AMPK, insulin has been shown to promote the uptake of energy-generating molecules such as glucose and fatty acids (6, 9). However, the information on whether there is a direct linkage between AMPK, insulin, and L-carnitine transport in muscle cells is currently missing.