SUMMARY PARAGRAPH for SAM35
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 (8, 9, 1, 2, 3). Mdm10p, a protein first discovered for its role in mitochondrial morphology, also associates with the SAM complex (10).
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 (11). The SAM complex then mediates insertion of the proteins into the mitochondrial outer membrane (12). 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 (10). 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 (12). 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 (13).
Sam35p is an essential constituent of the SAM complex, but is not strongly conserved beyond the fungi although it has weak similarity to the mammalian mitochondrial protein metaxin (2, 1, 3). Its submitochondrial location is disputed: several initial studies identified it as a peripheral protein on the cytosolic face of the outer membrane (2, 1, 3) but a later study suggests that it is embedded in the outer membrane via protein-protein interactions with Sam50p and may extend into the intermembrane space (12). Sam35p has been shown to have a role in the recognition of beta-barrel precursor proteins. Temperature-sensitive sam35 mutants display decreased binding of precursor proteins to the SAM complex (14), and Sam35p binds directly to precursor proteins (2, 12). Both of these observations lend support to the idea that at least part of Sam35p is in the same environment as beta-barrel precursors (14, 12).
Last updated: 2009-03-17