Nat. Rev. Endocrinol. doi:10.1038/nrendo.2015.181 Figure 4 Cytosolic–mitochondrial NAD+/NADH shuttles in yeast and mammalian cells Figure 4 | Cytosolic–mitochondrial NAD+/NADH shuttles in yeast and mammalian cells. a | In mammals, NADH is transferred into the mitochondrion through either the G3P or malate–aspartate shuttles, as the mitochondrial inner membrane is impermeable to NADH. In the glycerol-3-phospate shuttle, NADH oxidation is coupled with the conversion of dihydroxyacetone phosphate to G3P. G3P can then transfer gained electrons to FAD producing FADH2, which is then oxidized via the mitochondrial electron transport chain. In the malate–aspartate shuttle, the oxidation of NADH in the mitochondrial intermembrane space is coupled to the reduction of oxaloacetate to malate. Malate can then enter mitochondria by crossing the mitochondrial membrane and oxidize back to oxaloacetate thereby producing NADH in the mitochondrial matrix. Oxaloacetate is then converted to aspartate, which is shuttled back to the cytosol. b | In yeast, NAD+ is imported into the mitochondria via the transport proteins Ndt1p and Ndt2p. These NAD+ carrier proteins import NAD+ into mitochondria by unidirectional transport or by exchange with intra-mitochondrially generated AMP and GMP. Abbreviations: α-KG, α-ketoglutarate; cAspAT, cytosolic/mitochondrial aspartate aminotransferase; DHAP, dihydroxyacetone phosphate; FAD, flavin adenine dinucleotide; G3P, glycerol-3-phosphate; GAA, glutamate aspartate antiporter; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; II, mitochondrial complex II; mAspAT, cytosolic/mitochondrial aspartate aminotransferase; MDH, malate dehydrogenase; MKA, malate α-ketoglutarate antiporter; NAD+, nicotinamide adenine dinucleotide. Menzies, K. J. et al. (2015) Protein acetylation in metabolism—metabolites and cofactors Nat. Rev. Endocrinol. doi:10.1038/nrendo.2015.181