A toxic fusion protein accumulating between the mitochondrial membranes inhibits protein assembly in vivo

When overexpressed in Saccharomyces cerevisiae, beta-galactosidase fusion p roteins directed to the mitochondria are toxic, preventing growth of yeast cells on non-fermentable carbon sources (Emr. S. D., Vassarotti, A., Garret t, J., Geller, B. L., Takeda, M., and Douglas, M. G. (1986) J, Cell Biol. 1 02, 523-533), We show that such fusion proteins interfere with the assembly of respiratory complexes in the mitochondrial inner membrane, without bloc king protein translocation. The gene YME1, encoding an ATP-dependent metall oprotease of the mitochondrial inner membrane, acts as a suppressor of this defect; a 3-fold overexpression of Yme1p is sufficient to restore respirat ory complex assembly and mitochondrial function. Detailed knowledge of the topology and effect of the toxic beta-galactosidase fusion proteins will pe rmit the identification and characterization of components that control pro tein sorting and protein assembly within the mitochondrial inner membrane.