Maestro of the SereNADe: SLC25A51 Orchestrates Mitochondrial NAD

Abstract

Recently, three groups, Girardi et al., Kory et al., and Luongo et al., independently identified solute carrier (SLC) 25A51 as the long-sought, major mitochondrial NAD⁺ transporter in mammalian cells. These studies not only deorphan an uncharacterized transporter of the SLC25A family, but also shed light on other aspects of NAD⁺ biology.

Keywords: NAD; SLC25A family; mitochondrial transporter; redox; respiration.

Figure 1.. NAD⁺ Exists in Distinct Pools within Cellular Compartments, Supporting Critical Functions.

Each pool is also interconnected through transporters. NAD⁺ in mitochondria is transported via the recently identified solute carrier (SLC) 25A51 embedded in the mitochondrial inner membrane. It is then reduced by the tricarboxylic acid (TCA) cycle to NADH, which supplies electrons to the electron transport chain (blue complexes I–V shown in the figure). Beyond this major function, mitochondrial NAD⁺ has other metabolic and signaling roles. Cytosolic NAD⁺ supports many metabolic processes, including glycolysis. In the nucleus, NAD⁺ serves as a substrate for poly-(ADP-ribose) polymerase (PARP) and sirtuins. NAD⁺ also functions in other cellular compartments beyond those depicted.