The molecular mechanisms determining mitochondrial architecture are largely unclear. The C-terminal domain of Fcj1 and the TOB complex are shown to interact. Both are important for determining cristae morphology. The results explain how crista junctions are positioned at the outer membrane, assigning novel functions to both Fcj1 and the TOB complex.

The mitochondrial import receptor Tom70 and outer membrane protein Mim1 regulate recognition and insertion of the multispan protein Ugo1.

Proteins residing in the mitochondrial outer membrane facilitate various interactions between the organelle and the rest of the eukaryotic cell. All these proteins are encoded in the nucleus and synthesized on cytosolic ribosomes. Thus, they have to bear appropriate signals that ensure both their correct import into the organelle and their ability to acquire different topologies in the lipid bilayer. None of these proteins contain a canonical cleavable N-terminal presequence. Rather, the targeting and sorting signals can be found at their termini or in internal structural elements. In this review, we summarize the current knowledge regarding the diverse molecular mechanisms by which mitochondrial outer membrane proteins are specifically targeted to the organelle and inserted into the target membrane. Recognition events in the diverse pathways and the driving force for the various stages of this process will be discussed. This article is part of a Special Issue entitled Protein translocation across or insertion into membranes.

The TOM complex is the general mitochondrial entry site for newly synthesized proteins. Precursors of ␤-barrel proteins initially follow this common pathway and are then relayed to the SAM/TOB complex, which mediates their integration into the outer membrane. Three proteins, Sam50 (Tob55), Sam35 (Tob38/Tom38), and Sam37 (Mas37), have been identified as the core constituents of the latter complex. Sam37 is essential for growth at elevated temperatures, but the function of the protein is currently unresolved. To identify interacting partners of Sam37 and thus shed light on its function, we screened for multicopy suppressors of sam37⌬. We identified the small subunit of the TOM complex, Tom6, as such a suppressor and found a tight genetic interaction between the two proteins. Overexpression of SAM37 suppresses the growth phenotype of tom6⌬, and cells lacking both genes are not viable. The ability of large amounts of Tom6 to suppress the sam37⌬ phenotype can be linked to the capacity of Tom6 to stabilize Tom40, an essential ␤-barrel protein which is the central component of the TOM complex. Our results suggest that Sam37 is required for growth at higher temperatures, since it enhances the biogenesis of Tom40, and this requirement can be overruled by improved stability of newly synthesized Tom40 molecules.