Mitochondrial NAD⁺ gradient sustained by membrane potential and transport.

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. In this work, mutational analyses and localized NAD⁺ biosensors revealed that the mitochondrial membrane potential (ΔΨm) works in concert with charged residues in the carrier's inner pore to enable sustained import of NAD⁺ against its electrochemical gradient into the matr

SUBMITTER: Goyal S 

PROVIDER: S-EPMC12637306 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature