IMPORT INTO MITOCHONDRIA, FOLDING AND RETROGRADE MOVEMENT OF FUMARASEIN YEAST

A single translation product of the FUM1 gene encoding fumarase is dis tributed between the cytosol and mitochondria of Saccharomyces cerevis iae. All fumarase translation products are targeted and processed in m itochondria before distribution. Here we show that targeting of fumara se is coupled to translation and initially involves insertion of the p rotein across the mitochondrial membranes and processing by the matrix protease, Rapid folding of fumarase may determine its requirement for coupling of its translocation with translation and unique route of di stribution. The amino termini of most fumarase molecules are transloca ted across the mitochondrial membranes and processed. Unlike the in vi vo situation where these molecules are released into the cytosol, in v itro they remain externally attached to the mitochondria, thereby posi tioned for release from the organelle. Our model suggests that fumaras e displays a unique mechanism of targeting and distribution, which occ urs cotranslationally and involves folding and retrograde movement of the processed protein back through the translocation pore.