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Updated: Jul 21, 2026

Growth-based Determination and Biochemical Confirmation of Genetic Requirements for Protein Degradation in Saccharomyces cerevisiae
Published on: February 16, 2015
A role for ubiquitination in mitochondrial inheritance in Saccharomyces cerevisiae
1University of California, San Diego, Department of Biology, La Jolla, California 92093, USA.
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.
Insights
The smm1 mutation in yeast reveals that the Rsp5p ubiquitin ligase is crucial for mitochondrial inheritance. Protein ubiquitination is essential for maintaining proper mitochondrial function and distribution.
Area of Science:
- Cell Biology
- Genetics
- Biochemistry
Background:
- Mitochondrial distribution and morphology are critical for cellular function.
- The mdm1-252 mutation in Saccharomyces cerevisiae causes defects in mitochondrial inheritance.
- Understanding the genetic and molecular mechanisms regulating mitochondrial inheritance is essential.
Purpose of the Study:
- To investigate the role of the smm1 mutation in suppressing mitochondrial defects.
- To identify the gene responsible for the smm1 mutation and elucidate its function.
- To determine the involvement of protein ubiquitination in mitochondrial inheritance.
Main Methods:
- Genetic screening for suppressors of mdm1-252 defects.
- Gene mapping and identification of the smm1 locus.
- Analysis of yeast growth, mitochondrial morphology, and inheritance.
- Ubiquitin-protein ligase activity assays.
- Site-directed mutagenesis and gene overexpression studies.
Main Results:
- The smm1 mutation suppresses mdm1-252-induced mitochondrial defects.
- smm1 maps to RSP5, encoding the essential ubiquitin-protein ligase Rsp5p.
- Rsp5p's ligase activity is essential for mitochondrial inheritance.
- Overexpression of wild-type ubiquitin suppresses smm1 defects, while a K63R mutant ubiquitin exacerbates them.
- A second suppressor, smm2, maps to BUL1, a Rsp5p-interacting protein.
Conclusions:
- Protein ubiquitination mediated by Rsp5p is essential for mitochondrial inheritance in yeast.
- Rsp5p plays a critical role in regulating mitochondrial distribution and morphology.
- This study reveals a novel function for protein ubiquitination in cellular processes.
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