SUMMARY PARAGRAPH for TOM5
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 3, 4 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 TOM complex
The first step of import is mediated by the translocase of the outer mitochondrial membrane (TOM) complex, composed of the subunits Tom70p, Tom40p, Tom22p, Tom20p, Tom7p, Tom6p, and Tom5p (5, 6). Tom70p and Tom20p are both integral membrane proteins with cytosolic domains that act as receptors for incoming proteins. Tom70p interacts with hydrophobic precursor proteins via its tetratricopeptide repeats (7), while Tom20p interacts with precursor proteins that have N-terminal mitochondrial targeting signals (8). Tom70p also interacts with cytosolic Hsp70 family chaperones of the Ssa subfamily in order to receive preproteins from these chaperones (9). Tom40p and the three small (50-70 residues) proteins Tom5p, Tom6p, and Tom7p comprise the membrane pore for protein translocation, often referred to as the general import pore or GIP (6, 10). Tom40p has a beta-barrel structure and forms the membrane pore (11, 12, 13). The three small proteins are individually dispensable for function of the pore, but at least one of the three is absolutely required (1, 14). Tom22p appears to have a structural role in the complex and may also contribute to binding of precursor proteins on the outer surface of the organelle (15).
Although proteins destined for different mitochondrial compartments are imported by several different pathways, most or all of them traverse the outer membrane via the TOM complex. Transit through the TOM complex is sufficient for import of some outer membrane proteins, and of intermembrane space (IMS) proteins that are imported by a "folded trap" mechanism. In this mechanism, after the imported protein enters the IMS, intramolecular disulfide bonds form that lock it in a folded conformation and prevent its movement back out to the cytosol. Other types of incoming proteins are directed to other complexes after exiting the TOM complex. Incoming beta-barrel proteins are transferred to the SAM/TOB complex of the outer membrane, in a process involving the small TIM protein complexes of the IMS (Tim8p-Tim13p and Tim9p-Tim10p), and then inserted into the outer membrane. Matrix proteins and some inner membrane proteins are imported through the TOM complex and then the inner membrane TIM23 complex, which interact to form a supercomplex (16). Other inner membrane proteins are imported via the TOM complex and escorted across the IMS by the small TIM proteins to the inner membrane TIM22 complex, which mediates their integration into the inner membrane.
About the small TOM proteins
The roles of the small TOM proteins, Tom5p, Tom7p, and Tom6p, remain unclear. They are all anchored in the outer membrane via their carboxy termini (6). Tom5p has a negatively charged N-terminal domain exposed to the cytosol and it may be involved in transferring preproteins from their receptors, Tom20p and Tom70p, to the pore-forming Tom40p (1). The other two proteins, Tom6p and Tom7p, seem to be involved in assembly of the TOM complex and are required for its stability. A single tom5, tom6, or tom7 null mutation has only minor effects, but a triple null mutation is lethal (17, 14).
Last updated: 2009-03-17