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. 2018 Jan 20;28(3):180–212. doi: 10.1089/ars.2017.7120

FIG. 7.

FIG. 7.

Shuttling NADH into the mitochondria. (A) The malate–aspartate shuttle is the main NADH translocating apparatus in mammalian cells. cMDH first transfers electrons from NADH to malate, which can enter the mitochondria via the α-ketoglutarate/malate antiporter (SLC25A11). Once inside, mMDH oxidizes malate to regenerate NADH, which can then supply electrons to Complex I. The cycle is completed by the coupled transamination of OAA to form ASP by mAST (GOT2). Aspartate leaves the mitochondria by a calcium-dependent aspartate/glutamate antiporter and is converted back to OAA by GOT1. These reactions are supported by GLU and αKG cycling. (B) NADH can also transfer electrons directly into the electron transport chain through the glycerophosphate shuttle. In this cycle, cytoplasmic GPDH oxidizes NADH to generate G3P and DHAP. G3P is then oxidized by mitochondrial GPDH thereby transferring electrons to ubiquinone via and FAD cofactor. αKG, α-ketoglutarate; ASP, aspartate; cMDH, cytoplasmic malate dehydrogenase; DHAP, dihydroxyacetone phosphate; FAD, flavin adenine dinucleotide; G3P, glycerol-3-phosphate; GLU, glutamate; GPDH, glycerol-3-phosphate dehydrogenase; mAST, mitochondrial aspartate aminotransferase; mMDH, mitochondrial malate dehydrogenase; OAA, oxaloacetate.