TOM5 FUNCTIONALLY LINKS MITOCHONDRIAL PREPROTEIN RECEPTORS TO THE GENERAL IMPORT PORE

Most mitochondrial proteins are synthesized as preproteins on cytosoli c polysomes and are subsequently imported into the organelle(1-3). The mitochondrial outer membrane contains a multisubunit preprotein trans locase (Tom) which has receptors on the cytosolic side and a general i mport pore (GIP) in the membrane. Tom20-Tom22 and Tom70-Tom37 function as import receptors(4-7) with a preference for preproteins that have amino-terminal presequences or internal targeting information, respect ively. Tom40 is an essential constituent of the GIP(8,9), whereas Tom6 and Tom7 modulate the assembly and dissociation of the Tom machinery( 10,11). Here we report the identification of Tom5, a small subunit tha t has a crucial role importing preproteins destined for all four mitoc hondrial subcompartments. Tom5 has a single membrane anchor and a cyto solic segment with a negative net charge, and accepts preproteins from the receptors and mediates their insertion into the GIP. We conclude that Tom5 represents a functional link between surface receptors and G IP, and is part of an 'acid chain'(5) that guides the stepwise transpo rt of positively charged mitochondrial targeting sequences.