SUMMARY PARAGRAPH for SAM37
About mitochondrial import
While the mitochondrial genome encodes a handful of proteins, most of the hundreds of proteins that reside in the mitochondrion are encoded by nuclear genes, translated in the cytoplasm, and imported into mitochondria via a series of complex molecular machines (see 6, 7 for review). Many of the proteins imported into mitochondria are involved in respiration, which is not an essential process: S. cerevisiae is able to carry out either fermentative growth on carbon sources such as glucose, or respiratory growth on nonfermentable carbon sources such as glycerol and ethanol. However, since maintenance of the mitochondrial compartment is essential to life, mutations that completely disrupt mitochondrial import are lethal.
about the SAM complex
The sorting and assembly machinery (SAM) complex, also known as the translocase of outer membrane beta-barrel proteins (TOB), is required for the correct insertion of beta-barrel proteins into the mitochondrial outer membrane (8). The core of this complex, which is located in the outer membrane, is composed of Sam50p/Tob55p, itself a beta-barrel protein; Sam37p/Mas37p; and Sam35p/Tob38p (9, 4, 10, 11, 12). Mdm10p, a protein first discovered for its role in mitochondrial morphology, also associates with the SAM complex (13).
Beta-barrel proteins are first translocated across the outer membrane by the translocase of the outer mitochondrial membrane (TOM) complex. After transit through the TOM complex into the intermembrane space, both of the complexes of small TIM proteins that reside there (Tim8p-Tim13p complex and Tim9p-Tim10p) are involved in delivery of the beta-barrel proteins to the SAM complex (14). The SAM complex then mediates insertion of the proteins into the mitochondrial outer membrane (15). The final steps of the process require Mdm10p as well as two other proteins implicated in maintenance of mitochondrial morphology, Mdm12p and Mmm1p, which themselves form a complex with Mdm10p (13). In addition to Sam50p/Tob55p, the beta-barrel proteins imported by this route include porin (Por1p or VDAC), the most abundant outer membrane protein; Mdm10p; and Tom40p, which comprises the pore of the TOM complex. All of these substrate proteins have a SAM complex recognition motif termed the beta-signal (15). The SAM complex is also required for correct insertion of some other subunits of the TOM complex, which do not have a beta-barrel structure, into the outer membrane: the entire complex is required for assembly of Tom22p into the TOM complex, while Sam37p only is required for assembly of Tom5p, Tom6p, and Tom7p (16).
Sam37p is exposed to the cytosolic face of the outer membrane (2, 4). It is not an essential component of the SAM complex but does contribute to its function, since the sam37 null mutant displays reduced import of beta-barrel proteins (4, 17, 11). Sam37p is not strongly conserved beyond the fungi (2). Its major function seems to be maintenance of the stability of the SAM complex, and it may also affect release of proteins from the complex (17).
Last updated: 2009-03-17