The citrate-malate shuttle is a series of chemical reactions, commonly referred to as a biochemical cycle or system, that transports acetyl-CoA in the mitochondrial matrix across the inner and outer mitochondrial membranes for fatty acid synthesis. Mitochondria are enclosed in a double membrane. As the inner mitochondrial membrane is impermeable to acetyl-CoA, the shuttle system is essential to fatty acid synthesis in the cytosol. It plays an important role in the generation of lipids in the liver (hepatic lipogenesis).
The name of the citrate-malate shuttle is derived from the two intermediates – short-lived chemicals that are generated in a reaction step and consumed entirely in the next – citrate and malate that carry the acetyl-CoA molecule across the mitochondrial double membrane.
The citrate–malate shuttle is present in humans and other higher eukaryotic organisms and is closely related to the Krebs cycle. The system is responsible for the transportation of malate into the mitochondrial matrix to serve as an intermediate in the Krebs cycle and the transportation of citrate into the cytosol for secretion in Aspergillus niger, a fungus used in the commercial production of citric acid.