The Mitochondrial Disulfide Relay System: Roles in Oxidative Protein Folding and Beyond
Figure 1
Substrates and general outline of the mitochondrial disulfide relay. (a) Mia40 substrates can be classified into three groups: (1) members of the twin-CX9C and twin-CX3C family, respectively. Members of both families rely on four cysteines localized within two -helices for proper import. (2) The proteins scCcs1, scSod1, scAtp23, and Erv1/ALR form a second group of substrates with more complex folds and disulfide patterns. So far no common signal for the interaction with Mia40 has been identified in these proteins. (3) The two MTS-containing Mia40 substrates Tim22 and scMia40 are imported in a membrane potential-dependent manner and require Mia40 for proper folding only. (b) General outline of oxidative folding in the IMS. During substrate oxidation electrons are transferred from the substrate to Mia40. To reoxidize Mia40 electrons are transferred further via ALR to cytochrome (Cyt ) and then to cytochrome oxidase. Molecular oxygen (O2) is used as final electron acceptor to finally yield water (H2O).
