Neisserial Omp85 Protein Is Selectively Recognized and Assembled into Functional Complexes in the Outer Membrane of Human Mitochondria

As a consequence of their bacterial origin, mitochondria contain beta-barrel proteins in their outer membrane (OMM). These proteins require the translocase of the outer membrane (TOM) complex and the conserved sorting and assembly machinery (SAM) complex for transport and integration into the OMM. The SAM complex and the beta-barrel assembly machinery (BAM) required for biogenesis of beta-barrel proteins in bacteria are evolutionarily related. Despite this homology, we show that bacterial beta-barrel proteins are not universally recognized and integrated into the OMM of human mitochondria. Selectivity exists both at the level of the TOM and the SAM complex. Of all of the proteins we tested, human mitochondria imported only beta-barrel proteins originating from Neisseria sp., and only Omp85, the central component of the neisserial BAM complex, integrated into the OMM. PorB proteins from different Neisseria, although imported by the TOM, were not recognized by the SAM complex and formed membrane complexes only when functional Omp85 was present at the same time in mitochondria. Omp85 alone was capable of integrating other bacterial beta-barrel proteins in human mitochondria, but could not substitute for the function of its mitochondrial homolog Sam50. Thus, signals and machineries for transport and assembly of beta-barrel proteins in bacteria and human mitochondria differ enough to allow only a certain type of beta-barrel proteins to be targeted and integrated in mitochondrial membranes in human cells.