SLC25A51 is a Mitochondrial NAD Transporter

Tissue nicotinamide adenine dinucleotide (NAD) levels correlate with healthspan in laboratory rodents, falling with age or disease, and rising with exercise or caloric restriction. Moreover, the demonstration that supplemental NAD precursors confer beneficial effects in a variety of rodent models has led to a resurgence in interest in the basic biology of this molecule. Although it is widely recognized that NAD is present in the mitochondrial matrix and critical to the function of the organelle, the source of mitochondrial NAD has been debated. We recently used an isotopic labeling approach to demonstrate that direct uptake of intact NAD is one mechanism by which mitochondria are able to obtain this dinucleotide. Here, we identify SLC25A51 as a carrier that can mediate the transport of NAD across mitochondrial membranes. Compartment‐specific regulation of NAD concentration is an understudied process that likely plays crucial roles in the adaptation of cells and tissues to a changing metabolic environment. This work may ultimately reveal new therapeutic avenues to improve mitochondrial function.