Xiaolu A. Cambronne

Abstract SLC25A51 is required for the replenishment of free nicotinamide adenine dinucleotide (oxidized form) (NAD+) into mammalian mitochondria. However, it is not known how SLC25A51 imports this anionic molecule to sustain elevated NAD+ concentrations in the matrix. Understanding this would reveal regulatory mechanisms used to maintain critical bioenergetic gradients for cellular respiration, oxidative mitochondrial reactions, and mitochondrial adenosine triphosphate (ATP) production.

Abstract Nicotinamide adenine dinucleotide (NAD+) precursor supplementation shows metabolic and functional benefits in rodent models of disease and is being explored as potential therapeutic strategy in humans. However, the wide range of processes that involve NAD+ in every cell and subcellular compartment make it difficult to narrow down the mechanisms of action. Here we show that the rate of liver regeneration is closely associated with the concentration of NAD+ in hepatocyte mitochondria.

The development of biosensors has been slowed by the optimization required for each new iteration. Now, the ChemoX platform facilitates the expansion of sensor design, resulting in unique Förster resonance energy transfer pairings with versatile applications and optimized readouts. In this issue of Nature Chemical Biology, Hellweg et al.7 describe ChemoX, a new platform that enables the design of sensors with near-quantitative FRET ratios and clearer analyte-dependent readouts.