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J Biol Chem, Vol. 273, Issue 40, 25587-25593, October 2, 1998
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From the A single translation product of the
FUM1 gene encoding fumarase is distributed between the
cytosol and mitochondria of Saccharomyces cerevisiae. All
fumarase translation products are targeted and processed in
mitochondria before distribution. Here we show that targeting of
fumarase is coupled to translation and initially involves insertion of
the protein 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 distribution. The amino termini of most fumarase
molecules are translocated across the mitochondrial membranes and
processed. Unlike the in vivo situation where these molecules are released into the cytosol, in vitro they
remain externally attached to the mitochondria, thereby positioned for release from the organelle. Our model suggests that fumarase displays a
unique mechanism of targeting and distribution, which occurs cotranslationally and involves folding and retrograde movement of the
processed protein back through the translocation pore.
Department of Molecular Biology, Hebrew
University Medical School, Jerusalem 91120, Israel and the
¶ Institut Physiologische Chemie, Universitat Munchen,
Goethestrasse 33, 80336 Munchen, Germany
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