Related Experiment Video
Updated: Jan 19, 2026
Analysis of the Expression and Complexes Assembly of the Mitochondrial Respiratory Chain Proteins in the Fission Yeast Schizosaccharomyces pombe
Published on: May 2, 2025
Mrx6 regulates mitochondrial DNA copy number in Saccharomyces cerevisiae by engaging the evolutionarily conserved Lon
Aylin Göke1, Simon Schrott2, Arda Mizrak3
1Howard Hughes Medical Institute and Department of Biochemistry and Biophysics and.
Abstract:
Mitochondrial function depends crucially on the maintenance of multiple mitochondrial DNA (mtDNA) copies. Surprisingly, the cellular mechanisms regulating mtDNA copy number remain poorly understood. Through a systematic high-throughput approach in Saccharomyces cerevisiae, we determined mtDNA-to-nuclear DNA ratios in 5148 strains lacking nonessential genes. The screen revealed MRX6, a largely uncharacterized gene, whose deletion resulted in a marked increase in mtDNA levels, while maintaining wild type-like mitochondrial structure and cell size. Quantitative superresolution imaging revealed that deletion of MRX6 alters both the size and the spatial distribution of mtDNA nucleoids. We demonstrate that Mrx6 partially colocalizes with mtDNA within mitochondria and interacts with the conserved Lon protease Pim1 in a complex that also includes Mam33 and the Mrx6-related protein Pet20. Acute depletion of Pim1 phenocopied the high mtDNA levels observed in Δmrx6 cells. No further increase in mtDNA copy number was observed upon depletion of Pim1 in Δmrx6 cells, revealing an epistatic relationship between Pim1 and Mrx6. Human and bacterial Lon proteases regulate DNA replication by degrading replication initiation factors, suggesting a model in which Pim1 acts similarly with the Mrx6 complex, providing a scaffold linking it to mtDNA.
Insights
Researchers discovered that deleting the MRX6 gene significantly increases mitochondrial DNA (mtDNA) copy number in yeast. This finding sheds light on the poorly understood mechanisms regulating mtDNA levels and mitochondrial health.
Area of Science:
- Cell Biology
- Mitochondrial Biology
- Genetics
Background:
- Mitochondrial function relies on maintaining numerous mitochondrial DNA (mtDNA) copies.
- Cellular mechanisms governing mtDNA copy number regulation are not well understood.
Purpose of the Study:
- To systematically identify genes involved in regulating mitochondrial DNA copy number.
- To elucidate the function of the uncharacterized gene MRX6 in mtDNA maintenance.
Main Methods:
- Conducted a high-throughput screen of 5148 nonessential gene deletion strains in Saccharomyces cerevisiae.
- Quantified mtDNA-to-nuclear DNA ratios.
- Utilized quantitative superresolution imaging to analyze mtDNA nucleoid distribution.
- Investigated protein interactions and genetic epistasis using techniques like co-localization and protein depletion.
Main Results:
- Deletion of MRX6 led to a significant increase in mtDNA copy number without affecting mitochondrial structure or cell size.
- MRX6 deletion altered the size and spatial distribution of mtDNA nucleoids.
- Mrx6 interacts with the Lon protease Pim1, Mam33, and Pet20 within mitochondria.
- Pim1 depletion phenocopied the high mtDNA levels of Δmrx6 cells, and Pim1 and MRX6 exhibit an epistatic relationship.
Conclusions:
- MRX6 plays a critical role in regulating mtDNA copy number.
- The Mrx6 complex, potentially involving Pim1, may regulate mtDNA replication, similar to how Lon proteases function in bacteria and humans.
- This study provides novel insights into the molecular machinery controlling mitochondrial DNA homeostasis.
Related Concept Videos
02:23Abnormal Proliferation
02:53Conservative Site-specific Recombination and Phase Variation
The recognition sites for Cre recombinase called LoxP...
02:59Animal Mitochondrial Genetics
01:23Negative Regulator Molecules