MIA40 circumvents the folding constraints imposed by TRIAP1 function.

ABSTRACT: The MIA40 relay system mediates the import of small cysteine-rich proteins into the intermembrane mitochondrial space (IMS). MIA40 substrates are synthesized in the cytosol and assumed to be disordered in their reduced state in this compartment. As they cross the outer mitochondrial membrane, MIA40 promotes the oxidation of critical native disulfides to facilitate folding, trapping functional species in the IMS. Here, we study the redox-controled folding of TRIAP1, a small cysteine-rich protein with moonlighting function: regulating phospholipid trafficking between mitochondrial membranes in the IMS and preventing apoptosis in the cytosol. TRIAP1 dysregulation is connected to oncogenesis. Although TRIAP1 contains a canonical twin CX9C motif, its sequence characteristics and folding pathway

SUBMITTER: Pujols J 

PROVIDER: S-EPMC11930124 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature