Specific targeting of ISP6 to mitochondria is mediated by sequences other than its amino terminus

Most proteins synthesized in cytoplasm target to mitochondria through sequences at their amino termini. However, a previous study suggests that the native carboxyl terminus of ISP6 might be critical for its specific delivery. Here we investigated the sequence directing ISP6 to yeast mitochondrial outer membrane. Unlike mitochondrial presequences, a region at the amino terminus of ISP6 is dispensable for importing the rest of the protein. The carboxyl-terminal end and the nearby transmembrane region of ISP6 are essential to direct the protein exclusively to its correct membrane destination. ISP6 thus may be directed to mitochondria by an unusual sequence.