Mitochondria Can Directly Import NAD+ Through an Unknown Transporter: Preclinical Findings

Synopsis

Mitochondrial NAD+ is essential for choosing energy sources, maintaining daily rhythms, and helping cells survive stress. Scientists have debated whether mitochondria make NAD+ from cytosolic nicotinamide (NAM), NMN, or import NAD+ itself. This study shows that both mouse and human mitochondria can directly take up intact NAD+. Isolated mitochondria cannot make NAD+ from NAM, and while they can synthesize NAD+ from NMN, it doesn’t reach the mitochondrial matrix or efficiently support energy production. Experiments with labeled nicotinamide riboside (NR) confirmed that NAD+ itself enters mitochondria. These findings suggest there is an unknown NAD+ transporter in mitochondria, challenging the long-held idea that the mitochondrial inner membrane is impermeable to NAD+ and NADH.

Journal

eLife