malateaspartate

The malate–aspartate shuttle, or malate-aspartate shuttle, is a biochemical system that transfers reducing equivalents from cytosolic NADH into the mitochondrial matrix, enabling efficient ATP production by oxidative phosphorylation. It operates primarily in tissues with high oxidative demand, such as the liver, heart, kidney, and brain.

The shuttle relies on a sequence of enzymatic and transporter steps. In the cytosol, oxaloacetate is reduced to malate by cytosolic malate dehydrogenase, consuming NADH. Malate is transported into the mitochondrial matrix by a malate–α-ketoglutarate antiporter. Inside the matrix, malate is oxidized back to oxaloacetate by mitochondrial malate dehydrogenase, producing NADH in the matrix. Oxaloacetate is then transaminated to aspartate by mitochondrial aspartate aminotransferase, using glutamate to form α-ketoglutarate. Aspartate is shuttled back to the cytosol in exchange for malate via an aspartate–glutamate transporter, and cytosolic aspartate is converted to oxaloacetate, completing the cycle. The net effect is transfer of cytosolic reducing equivalents into the mitochondrial NADH pool.

This shuttle is more energy-efficient than the glycerol-3-phosphate shuttle, yielding more ATP per cytosolic NADH. Its performance depends on mitochondrial function and transporter activity, and it can be modulated in metabolic states such as ischemia, hypoxia, or diseases affecting mitochondrial metabolism.