A role for ubiquitination in mitochondrial inheritance in Saccharomyces cerevisiae

H A Fisk1, M P Yaffe

  • 1University of California, San Diego, Department of Biology, La Jolla, California 92093, USA.

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.

Related Concept Videos

Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
Animal Mitochondrial Genetics02:59

Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
Export of Mitochondrial and Chloroplast Genes02:19

Export of Mitochondrial and Chloroplast Genes

A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred irrespective...
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...