Fig. 1.

Two-tier experimental strategy for the analysis of proteome-wide protein–protein interactions in BHM. Mitochondria membranes were cross-linked with either of the three cross-linking reagents, DSSO, PhoX, or DMTMM. Subsequently, samples were analyzed by XL-MS and complexome profiling. Identified cross-linked peptides were used to generate protein–protein interaction networks. Protein interactions and structural models of AIFM1 with COX were then computationally modeled using the distance restraints from XL-MS data together with the assembly state and stoichiometry information obtained by complexome profiling.