Dbi1 is an oxidoreductase and an assembly chaperone for mitochondrial inner membrane proteins

Import and assembly of mitochondrial proteins into multimeric complexes are essential for cellular function. Yet, many steps of these processes and the proteins involved remain unknown. Here, we identify a novel pathway for disulfide bond formation and assembly of mitochondrial inner membrane (IM) proteins. Dbi1, a previously uncharacterized IM protein, interacts with an unassembled pool of Tim17, the central subunit of the presequence translocase of the IM, and is upregulated in cells with increased levels of unassembled Tim17. In the absence of Dbi1, conformation of the presequence translocase is affected and stability of Tim17 is reduced. Furthermore, Dbi1, through its conserved CxxC motif, is involved in formation of the disulfide bond in Tim17 in a manner independent of the disulfide-relay system, the major oxidation-driven protein import pathway into mitochondria. The substrate spectrum of Dbi1 is not limited to Tim17 but includes at least two more IM proteins, Tim22 and Cox20. We conclude that Dbi1 is a novel oxidoreductase in mitochondria which introduces disulfide bonds into IM proteins and chaperones their assembly into multimeric protein complexes.