A role for ubiquitination in mitochondrial inheritance in Saccharomyces cerevisiae.
The smm1 mutation suppresses defects in mitochondrial distribution and morphology caused by the mdm1-252 mutation in the yeast Saccharomyces cerevisiae. Cells harboring only the smm1 mutation themselves display temperature-sensitive growth and aberrant mitochondrial inheritance and morphology at the nonpermissive temperature. smm1 maps to RSP5, a gene encoding an essential ubiquitin-protein ligase. The smm1 defects are suppressed by overexpression of wild-type ubiquitin but not by overexpression of mutant ubiquitin in which lysine-63 is replaced by arginine. Furthermore, overexpression of this mutant ubiquitin perturbs mitochondrial distribution and morphology in wild-type cells. Site-directed mutagenesis revealed that the ubiquitin ligase activity of Rsp5p is essential for its function in mitochondrial inheritance. A second mutation, smm2, which also suppressed mdm1-252 defects, but did not cause aberrant mitochondrial distribution and morphology, mapped to BUL1, encoding a protein interacting with Rsp5p. These results indicate that protein ubiquitination mediated by Rsp5p plays an essential role in mitochondrial inheritance, and reveal a novel function for protein ubiquitination.
Fisk
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HA
University of California, San Diego, Department of Biology, La Jolla, California 92093, USA.
Yaffe
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MP
D048868:Adaptor Proteins, Signal Transducing; D019943:Amino Acid Substitution; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D020043:Genes, Essential / Q000235:genetics; D005800:Genes, Fungal / Q000235:genetics / Q000502:physiology; D016153:Genes, Suppressor / Q000235:genetics; D005816:Genetic Complementation Test; D007381:Intermediate Filament Proteins; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic; D013696:Temperature; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C099939:BUL1 protein, S cerevisiae; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; D007381:Intermediate Filament Proteins; C075618:MDM1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C469287:RSP5 protein, S cerevisiae