Abstract
As a consequence of their bacterial origin, mitochondria contain β-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 β-barrel assembly machinery (BAM) required for biogenesis of β-barrel proteins in bacteria are evolutionarily related. Despite this homology, we show that bacterial β-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 β-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 β-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 β-barrel proteins in bacteria and human mitochondria differ enough to allow only a certain type of β-barrel proteins to be targeted and integrated in mitochondrial membranes in human cells.
Highlights
-barrel assembly machinery; Blue native (BN), blue native; inner membrane (IMM), inner mitochondrial membrane; SAM, sorting and assembly machinery; TOB, topogenesis of outer membrane -barrel proteins; the outer mitochondrial membrane (TOM), translocase of outer membrane; VDAC, voltage-dependent anion-selective channel
A specific sequence in the C terminus of the protein is recognized by the -barrel assembly machinery (BAM), which integrates these proteins into the bacterial outer membrane [14]
Our results indicate that the human and yeast TOM and SAM complexes have diverged, as well as that neisserial Omp85 can function alone in the outer membrane (OMM), a possible important prerequisite for the evolution of mitochondrial OMM transport and assembly machineries
Summary
-barrel assembly machinery; BN, blue native; IMM, inner mitochondrial membrane; SAM, sorting and assembly machinery; TOB, topogenesis of outer membrane -barrel proteins; TOM, translocase of outer membrane; VDAC, voltage-dependent anion-selective channel. A specific signal has been identified in the C-terminal part of mitochondrial -barrel proteins that directs them to the SAM complex to be properly sorted and integrated into the OMM [12] Unlike in yeast, this signal in mammalian -barrel proteins is always present at the extreme C terminus of the protein, and the addition of even a short stretch of amino acids interferes with its recognition [13]. The major component of the BAM complex is YaeT/ BamA in Escherichia coli [15], or Omp85/BamA in Neisseria meningitidis [16] These proteins belong to the Omp family, a member of which is mitochondrial Sam50 [6]. In N. meningitidis these include accessory lipoproteins RmpM, BamC, ComL/BamD, and BamE [17]
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