Welcome to the Family: Identification of the NAD+ Transporter of Animal Mitochondria as Member of the Solute Carrier Family SLC25

Subcellular compartmentation is a fundamental property of eukaryotic cells. Communication and metabolic and regulatory interconnectivity between organelles require that solutes can be transported across their surrounding membranes. Indeed, in mammals, there are hundreds of genes encoding solute carriers (SLCs) which mediate the selective transport of molecules such as nucleotides, amino acids, and sugars across biological membranes. Research over many years has identified the localization and preferred substrates of a large variety of SLCs. Of particular interest has been the SLC25 family, which includes carriers embedded in the inner membrane of mitochondria to secure the supply of these organelles with major metabolic intermediates and coenzymes. The substrate specificity of many of these carriers has been established in the past. However, the route by which animal mitochondria are supplied with NAD(+) had long remained obscure. Only just recently, the existence of a human mitochondrial NAD(+) carrier was firmly established. With the realization that SLC25A51 (or MCART1) represents the major mitochondrial NAD(+) carrier in mammals, a long-standing mystery in NAD(+) biology has been resolved. Here, we summarize the functional importance and structural features of this carrier as well as the key observations leading to its discovery.

Automated summary

Subcellular compartmentation is a fundamental property of eukaryotic cells, where the transport of solutes across membranes plays a crucial role in cellular communication and metabolic regulation. In mammals, the SLC family comprises carriers that selectively transport molecules across biological membranes, with the SLC25 family playing a particularly important role in supplying mitochondria with metabolic intermediates. The recent discovery of SLC25A51 as the major mitochondrial NAD(+) carrier in mammals has resolved a long-standing mystery in NAD(+) biology.