Cyclophilin D is a new non-canonical substrate of the mitochondrial intermembrane space assembly pathway.

ABSTRACT: Mitochondrial protein import is essential for organelle function and cellular homeostasis. While Cyclophilin D (CypD) is a well-characterized regulator of the mitochondrial permeability transition pore (MPTP) and resides in the matrix, the mechanisms underlying its import remain poorly defined. In this study, we identify CypD as a novel non-canonical substrate of the mitochondrial intermembrane space assembly (MIA) pathway mediated by the oxidoreductase Mia40. Structural analysis revealed conserved cysteine pairs in CypD that are compatible with disulfide bond formation. Using in vitro pull-down assays, we demonstrate a redox-sensitive interaction between CypD and Mia40, which was further confirmed by co-immunoprecipitation and proximity ligation assays. Expression of CypD cysteine mutants

SUBMITTER: Equisoain Redin M 

PROVIDER: S-EPMC12732308 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature