Figure 1.

In the malate–aspartate shuttle (MAS) cytosolic malate dehydrogenase (MDHc) oxidizes NADH and converts oxaloacetate (OAA) to malate (top right of figure), which enters the mitochondria in exchange with α-ketoglutarate (α-KG). The mitochondrial malate dehydrogenase (MDHm) re-oxidizes malate to OAA, which is transaminated to aspartate by the mitochondrial aspartate aminotransferase (AATm). Aspartate leaves the mitochondria in exchange with glutamate, requiring ACG (aralar or citrin). In the mitochondria glutamate conversion to α-KG is essential for AATm activity forming aspartate from OAA and delivering α-KG for mitochondrial export. The glutamate imported into the mitochondria had been formed by cytosolic aspartate aminotransferase (AATc) from α-KG after its entry into the cytosol. Without MAS activity NADH formed in the cytosol during glycolysis would have been unable to enter the mitochondria for oxidation. Reprinted from Hertz and Dienel (69), with permission.