A toxic fusion protein accumulating between the mitochondrial membranes inhibits protein assembly in vivo.
When overexpressed in Saccharomyces cerevisiae, beta-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 beta-galactosidase fusion proteins will permit the identification and characterization of components that control protein sorting and protein assembly within the mitochondrial inner membrane.
Beilharz
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Department of Biochemistry, La Trobe University, Bundoora 3083, Australia.
Suzuki
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CK
Lithgow
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D049069:ATP-Dependent Proteases; D000251:Adenosine Triphosphatases; D001692:Biological Transport; D005656:Fungal Proteins / Q000096:biosynthesis; D007425:Intracellular Membranes / Q000187:drug effects*; D046911:Macromolecular Substances; D008928:Mitochondria / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000633:toxicity*; D011993:Recombinant Fusion Proteins / Q000633:toxicity*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic; D001616:beta-Galactosidase / Q000235:genetics / Q000633:toxicity*
D005656:Fungal Proteins; D046911:Macromolecular Substances; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D001616:beta-Galactosidase; D049069:ATP-Dependent Proteases; C082702:YME1 protein, S cerevisiae; D000251:Adenosine Triphosphatases; D006180:Proton-Translocating ATPases