Two Modular Forms of the Mitochondrial Sorting and Assembly Machinery Are Involved in Biogenesis of α-Helical Outer Membrane Proteins

• Published in: Journal of molecular biology 2010-02, Vol.396 (3), p.540-549
• Main Authors: Thornton, Nicolas, Stroud, David A., Milenkovic, Dusanka, Guiard, Bernard, Pfanner, Nikolaus, Becker, Thomas
• Format: Article
• Language: English
• Subjects: Macromolecular Substances - metabolism; Mdm10; Membrane Transport Proteins - metabolism; Mitochondria - metabolism; Mitochondria - physiology; Mitochondrial Membranes - metabolism; Mitochondrial Proteins - metabolism; Protein Precursors - metabolism; protein sorting; Protein Transport; Saccharomyces cerevisiae; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - physiology; Saccharomyces cerevisiae Proteins - metabolism; SAM complex; TOM complex
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2009.12.026

The mitochondrial outer membrane contains two translocase machineries for precursor proteins—the translocase of the outer membrane (TOM complex) and the sorting and assembly machinery (SAM complex). The TOM complex functions as the main mitochondrial entry gate for nuclear-encoded proteins, whereas the SAM complex was identified according to its function in the biogenesis of β-barrel proteins of the outer membrane. The SAM complex is required for the assembly of precursors of the TOM complex, including not only the β-barrel protein Tom40 but also a subset of α-helical subunits. While the interaction of β-barrel proteins with the SAM complex has been studied in detail, little is known about the interaction between the SAM complex and α-helical precursor proteins. We report that the SAM is not static but that the SAM core complex can associate with different partner proteins to form two large SAM complexes with different functions in the biogenesis of α-helical Tom proteins. We found that a subcomplex of TOM, Tom5–Tom40, associates with the SAM core complex to form a new large SAM complex. This SAM–Tom5/Tom40 complex binds the α-helical precursor of Tom6 after the precursor has been inserted into the outer membrane in an Mim1 (mitochondrial import protein 1)-dependent manner. The second large SAM complex, SAM–Mdm10 (mitochondrial distribution and morphology protein), binds the α-helical precursor of Tom22 and promotes its membrane integration. We suggest that the modular composition of the SAM complex provides a flexible platform to integrate the sorting pathways of different precursor proteins and to promote their assembly into oligomeric complexes.