The Interaction and Effect of a Small MitoBlock Library as Inhibitor of ALR Protein-Protein Interaction Pathway.

ABSTRACT: MIA40 and ALR of the MIA pathway mediate the import of protein precursors that form disulfides into the mitochondrial intermembrane space. This import pathway is suggested to be a linear pathway in which MIA40 first binds to the precursor via a disulfide linkage and oxidizes it. Subsequently, ALR re-oxidizes MIA40 and then ALR transfers electrons to terminal electron acceptors. However, the precise mechanism by which ALR and MIA40 coordinate translocation is unknown. With a collection of small molecule modulators (MB-5 to MB-9 and MB-13) that inhibit ALR activity, we characterized the import mechanism in mitochondria. NMR studies show that most of the compounds bind to a similar region in ALR. Mechanistic studies with small molecules demonstrate that treatment with compound MB-6 locks the

SUBMITTER: Muzzioli R 

PROVIDER: S-EPMC10816046 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature