Related Experiment Video
Updated: Sep 17, 2025
08:07
Analysis of the Expression and Complexes Assembly of the Mitochondrial Respiratory Chain Proteins in the Fission Yeast Schizosaccharomyces pombe
Published on: May 2, 2025
519
Ubp2 modulates DJ-1-mediated redox-dependent mitochondrial dynamics in Saccharomyces cerevisiae
Sananda Biswas1, Patrick D'Silva1
1Department of Biochemistry, Division of Biological Sciences, Indian Institute of Science (IISc), Bengaluru, Karnataka, India.
Plos Genetics
|July 3, 2025
Summary
Yeast DJ-1 paralogs and Ubp2 deubiquitinase genetically interact to maintain mitochondrial homeostasis. Loss of Ubp2 restores mitochondrial integrity and function in DJ-1 deficient cells, improving oxidative stress resistance.
Area of Science:
- Cell Biology
- Molecular Biology
- Neuroscience
Background:
- Mitochondrial integrity is vital for cellular health and neurological disorder pathogenesis.
- DJ-1 (PARK7) mutations disrupt mitochondrial homeostasis, linking it to Parkinson's disease.
- The precise molecular mechanisms of DJ-1 in mitochondrial maintenance are not fully understood.
Purpose of the Study:
- To elucidate the role of yeast DJ-1 paralogs (Hsp31 paralogs) in regulating mitochondrial homeostasis.
- To investigate the genetic and molecular interactions governing mitochondrial integrity.
- To understand the functional crosstalk between DJ-1 and deubiquitinating enzymes in cellular health.
Main Methods:
- Utilized Saccharomyces cerevisiae as a model organism.
- Performed genetic synthetic interaction analysis between Ubp2 and DJ-1 paralogs.
- Assessed mitochondrial morphology, Fzo1 ubiquitination, and mitophagic flux.
- Evaluated cellular resistance to oxidative stress.
Main Results:
- Identified a synthetic genetic interaction between Ubp2 and DJ-1 paralogs.
- Demonstrated that Ubp2 loss restores mitochondrial tubular networks in DJ-1 deletion mutants by modulating Fzo1 ubiquitination.
- Showed that Ubp2 deletion rescues mitochondrial respiration, functionality, and mitophagic flux in DJ-1 deficient cells.
- Found that Ubp2 deletion confers oxidative stress resistance independently of DJ-1 paralogs.
Conclusions:
- Deciphered the intricate mechanism of yeast DJ-1 paralogs in maintaining mitochondrial homeostasis.
- Established a novel functional crosstalk between Ubp2 and DJ-1 in regulating mitochondrial integrity and cellular health.
- Highlighted the therapeutic potential of targeting Ubp2-DJ-1 interactions for neurological disorders.
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