SUMMARY PARAGRAPH for SAM50
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 5, 6 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 (7). 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 (1, 8, 9, 10, 11). Mdm10p, a protein first discovered for its role in mitochondrial morphology, also associates with the SAM complex (12).
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 (13). The SAM complex then mediates insertion of the proteins into the mitochondrial outer membrane (14). 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 (12). 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 (14). 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 (15).
Sam50p is an essential constituent of the SAM complex and is conserved across prokaryotes and eukaryotes (1, 3). Conditional sam50 mutations selectively affect the import of beta-barrel proteins (1, 3, 16). Sam50p has a beta-barrel structure and also contains an N-terminal polypeptide transport-associated (POTRA) domain that is exposed to the intermembrane space. There is conflicting evidence on whether the N-terminal POTRA domain of Sam50p is involved in recognition of beta-barrel precursor proteins by the SAM complex, or whether Sam35p fills this role (17, 14). The role of Sam50p in the later steps of import is clear: the isolated protein can integrate into a lipid bilayer and form a functional channel in vitro, and is thought to act in vivo by allowing beta-barrel proteins to fold within its channel and then releasing them laterally into the outer membrane (3, 14).
Last updated: 2009-03-17