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J Biol Chem, Vol. 273, Issue 52, 35268-35272, December 25, 1998
From the When overexpressed in Saccharomyces
cerevisiae,
A Toxic Fusion Protein Accumulating between the Mitochondrial
Membranes Inhibits Protein Assembly in Vivo
,
Department of Biochemistry, La Trobe
University, Bundoora 3083, Australia and the § Department of
Biochemistry and Molecular Biology, University of Medicine and
Dentistry of New Jersey, Newark, New Jersey 07103
-galactosidase fusion proteins directed to the
mitochondria are toxic, preventing growth of yeast cells on
non-fermentable carbon sources (Emr, S. D., Vassarotti, A.,
Garrett, J., Geller, B. L., Takeda, M., and Douglas, M. G. (1986) J. Cell Biol. 102, 523-533). We show that such
fusion proteins interfere with the assembly of respiratory complexes in
the mitochondrial inner membrane, without blocking protein
translocation. The gene YME1, encoding an
ATP-dependent metalloprotease of the mitochondrial inner
membrane, acts as a suppressor of this defect; a 3-fold overexpression
of Yme1p is sufficient to restore respiratory complex assembly and
mitochondrial function. Detailed knowledge of the topology and effect
of the toxic -galactosidase fusion proteins will permit the
identification and characterization of components that control protein
sorting and protein assembly within the mitochondrial inner membrane.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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