Dynamics of SLC25A51 reveal preference for oxidized NAD⁺ and substrate led transport.

ABSTRACT: SLC25A51 is a member of the mitochondrial carrier family (MCF) but lacks key residues that contribute to the mechanism of other nucleotide MCF transporters. Thus, how SLC25A51 transports NAD⁺ across the inner mitochondrial membrane remains unclear. To elucidate its mechanism, we use Molecular Dynamics simulations to reconstitute SLC25A51 homology models into lipid bilayers and to generate hypotheses to test. We observe spontaneous binding of cardiolipin phospholipids to three distinct sites on the exterior of SLC25A51's central pore and find that mutation of these sites impairs cardiolipin binding and transporter activity. We also observe that stable formation of the required matrix gate is controlled by a single salt bridge. We identify binding sites in SLC25A51 for NAD^+</

SUBMITTER: Goyal S 

PROVIDER: S-EPMC10561365 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature