Abstract
The mitochondrial outer membrane contains two distinct machineries for protein import and protein sorting that function in a sequential manner: the general translocase of the outer membrane (TOM complex) and the sorting and assembly machinery (SAM complex), which is dedicated to beta-barrel proteins. The SAM(core) complex consists of three subunits, Sam35, Sam37, and Sam50, that can associate with a fourth subunit, the morphology component Mdm10, to form the SAM(holo) complex. Whereas the SAM(core) complex is required for the biogenesis of all beta-barrel proteins, Mdm10 and the SAM(holo) complex play a selective role in beta-barrel biogenesis by promoting assembly of Tom40 but not of porin. We report that Tom7, a conserved subunit of the TOM complex, functions in an antagonistic manner to Mdm10 in biogenesis of Tom40 and porin. We show that Tom7 promotes segregation of Mdm10 from the SAM(holo) complex into a low molecular mass form. Upon deletion of Tom7, the fraction of Mdm10 in the SAM(holo) complex is significantly increased, explaining the opposing functions of Tom7 and Mdm10 in beta-barrel sorting. Thus the role of Tom7 is not limited to the TOM complex. Tom7 functions in mitochondrial protein biogenesis by a new mechanism, segregation of a sorting component, leading to a differentiation of beta-barrel assembly.
Highlights
The mitochondrial outer membrane contains two distinct machineries for protein import and protein sorting that function in a sequential manner: the general translocase of the outer membrane (TOM complex) and the sorting and assembly machinery (SAM complex), which is dedicated to -barrel proteins
Whereas the SAMcore complex is required for sorting of all -barrel outer membrane proteins analyzed, the SAMholo complex is dedicated to assembly of the TOM complex, i.e. Mdm10 is selectively required for the final steps of assembly of Tom40 but not porin [34]
Because Mdm10 in the SAMholo complex is only required for the assembly of the TOM complex but not for other -barrel proteins like porin, the seemingly controversial effect of tom7⌬ mitochondria on the biogenesis of Tom40 and porin is explained by the antagonistic effect of Tom7 on Mdm10
Summary
Whereas the SAMcore complex is required for sorting of all -barrel outer membrane proteins analyzed, the SAMholo complex is dedicated to assembly of the TOM complex, i.e. Mdm is selectively required for the final steps of assembly of Tom but not porin [34]. Tom was found to function at the trans side of the TOM complex by increasing the efficiency of protein transport to internal mitochondrial compartments [42, 46, 51], but the strongest import defect of mitochondria lacking Tom was observed for the precursor of porin [42, 49, 53], indicating a role of Tom in biogenesis of outer membrane proteins. We show that Tom exerts an inhibitory effect on Mdm by promoting its segregation from the SAMholo complex into a low molecular mass form, implying a new mechanism for mitochondrial protein sorting
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