Shuttling Electron Carriers into the Mitochondrion

The inner mitochondrial membrane is impermeable to NADH. Electrons carried by NADH that are created in the cytoplasm (such as in glycolysis) must be shuttled into the mitochondrial matrix before they can enter the electron transport system (ETS).

This shuttle involves the reduction of a substrate by NADH molecules in the cytoplasm, passage of the reduced substrate into the mitochondrial matrix via a specific transport system, reoxidation of that compound inside the matrix, and passage of the oxidized substrate back to the cytoplasm, where it can undergo the same cycle again.

Figure 15.11a illustrates the dihydroxyacetone phosphate (DHAP)/glycerol-3-phosphate (Gly-3-P) shuttle system that is active in brain and in the flight muscle of insects. In the shuttle, NADH reduces DHAP to Gly-3-P. Gly-3-P donates electrons to Glycerol-3-phosphate dehydrogenase in the inner mitochondrial membrane, regenerating DHAP and converting FAD to FADH 2 in the process. Note that the shuttle transfers electrons from NADH ultimately to make FADH 2, which transfers electrons to CoQ, bypassing complex I. This process is inefficient, however, because electrons that are passed from NADH to complex I generate enough energy to make 3 ATPs per pair of electrons, but electrons entering after complex I only generate enough energy to make 2 ATPs.

Figure 15.11b shows the malate/aspartate shuttle system, which is particularly active in liver and heart. It uses malate, aspartate, and oxaloacetate to shuttle cytoplasmic electrons from NADH into the mitochondrial matrix. In this shuttle, NADH reduces oxaloacetate to malate, which travels through an inner membrane transport system that ultimately exchanges the malate for an -ketoglutarate. To do so, malate first donates electrons to NAD+, forming NADH and oxaloacetate in the process. Then, in order to regenerate the original substrates in their original locations, oxaloacetate is transaminated to aspartate by glutamate, which is simultaneously converted to -ketoglutarate. Aspartate is transported out of the mitochondrion in exchange for glutamate. Outside the mitochondrion, aspartate is converted to oxaloacetate by transaminating -ketoglutarate to glutamate. Unlike the DAHP/Gly-3-P shuttle, none of the energy of the electrons is wasted in the malate/aspartate shuttle, because the NADH generated inside the mitochondrial matrix passes electrons to complex I, enabling production of 3 ATPs per pair of electrons from NADH.

See also: Electron Transport, Mitochondrial Structure and Function