Separating mitochondrial protein assembly and endoplasmic reticulum tethering by selective coupling of Mdm10
Ellenrieder L, Opaliński Ł, Becker L, Krüger V, Mirus O, Straub SP, Ebell K, Flinner N, Stiller SB, Guiard B, Meisinger C, Wiedemann N, Schleiff E, Wagner R, Pfanner N, Becker T.
The mitochondrial distribution and morphology protein Mdm10 is a beta-barrel protein of the mitochondrial outer membrane and plays a central role for the biogenesis of mitochondria. It is a core component of the endoplasmic reticulum-mitochondria encounter structure (ERMES), which forms a molecular bridge between both cell organelles. Mdm10 further associates with the sorting and assembly machinery (SAM complex), which promotes biogenesis of mitochondrial outer membrane proteins. Loss of Mdm10 leads to multiple phenotypes including aberrant mitochondrial morphology, altered phospholipid composition of the mitochondrial membranes and impaired protein biogenesis. The functions of the individual Mdm10 populations remained poorly understood. Here, we identified distinct binding sites for SAM and ERMES complexes on the beta-barrel of Mdm10. We used point mutants of Mdm10 that selectively affect the interaction to ERMES or SAM for functional studies. We could should that Mdm10 forms the membrane anchor for the ERMES complex to maintain mitochondrial morphology and phospholipid homeostasis. Mdm10 forms a channel, which promotes outer membrane protein biogenesis at the SAM complex. Thus, coupling to different partner proteins enables Mdm10 to fulfill various functions for mitochondrial biogenesis.
