Mrx6 regulates mitochondrial DNA copy number in S. cerevisiae by engaging the evolutionarily conserved Lon protease Pim1
| Autor: | Simon Schrott, Vladislav Belyy, Christof Osman, Aylin Göke, Arda Mizrak, Peter Walter |
|---|---|
| Přispěvatelé: | Fox, Thomas D |
| Rok vydání: | 2020 |
| Předmět: |
Ribosomal Proteins
Mitochondrial DNA Saccharomyces cerevisiae Proteins DNA Copy Number Variations Evolution 1.1 Normal biological development and functioning Saccharomyces cerevisiae Mitochondrion Medical and Health Sciences Mitochondrial Proteins 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine ATP-Dependent Proteases Protein Domains Models Underpinning research Genetics Nucleoid Genetic Testing Molecular Biology Gene Conserved Sequence 030304 developmental biology 0303 health sciences biology Serine Endopeptidases DNA replication Molecular Cell Biology DNA Biological Sciences biology.organism_classification Biological Cell biology Mitochondria Mitochondrial chemistry Replication Initiation Generic health relevance 030217 neurology & neurosurgery Gene Deletion Protein Binding Developmental Biology |
| Zdroj: | Molecular Biology of the Cell Molecular biology of the cell, vol 31, iss 7 |
| ISSN: | 1059-1524 |
| DOI: | 10.1091/mbc.e19-08-0470 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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