A role for ubiquitination in mitochondrial inheritance in Saccharomyces cerevisiae

J Cell Biol. 1999 Jun 14;145(6):1199-208. doi: 10.1083/jcb.145.6.1199.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Substitution
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins*
  • Endosomal Sorting Complexes Required for Transport
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Expression
  • Genes, Essential / genetics
  • Genes, Fungal / genetics
  • Genes, Fungal / physiology
  • Genes, Suppressor / genetics
  • Genetic Complementation Test
  • Intermediate Filament Proteins
  • Ligases / genetics
  • Ligases / metabolism
  • Mitochondria / genetics
  • Mitochondria / physiology*
  • Mutation
  • Phenotype
  • Protein Binding
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins*
  • Suppression, Genetic
  • Temperature
  • Ubiquitin-Protein Ligase Complexes*
  • Ubiquitin-Protein Ligases
  • Ubiquitins / genetics
  • Ubiquitins / metabolism
  • Ubiquitins / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • BUL1 protein, S cerevisiae
  • Carrier Proteins
  • Cell Cycle Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Fungal Proteins
  • Intermediate Filament Proteins
  • MDM1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Ubiquitins
  • Ubiquitin-Protein Ligase Complexes
  • Ubiquitin-Protein Ligases
  • Ligases
  • RSP5 protein, S cerevisiae