Yeast Chromatin Mutants Reveal Altered mtDNA Copy Number and Impaired Mitochondrial Membrane Potential
Mitochondria are multifunctional, dynamic organelles important for stress response, cell longevity, ageing and death. Although the mitochondrion has its genome, nuclear-encoded proteins are essential in regulating mitochondria biogenesis, morphology, dynamics and function. Moreover, chromatin struct...
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MDPI AG
2023-03-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/9/3/329 |
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| author | Dessislava Staneva Bela Vasileva Petar Podlesniy George Miloshev Milena Georgieva |
| author_facet | Dessislava Staneva Bela Vasileva Petar Podlesniy George Miloshev Milena Georgieva |
| author_sort | Dessislava Staneva |
| collection | DOAJ |
| description | Mitochondria are multifunctional, dynamic organelles important for stress response, cell longevity, ageing and death. Although the mitochondrion has its genome, nuclear-encoded proteins are essential in regulating mitochondria biogenesis, morphology, dynamics and function. Moreover, chromatin structure and epigenetic mechanisms govern the accessibility to DNA and control gene transcription, indirectly influencing nucleo-mitochondrial communications. Thus, they exert crucial functions in maintaining proper chromatin structure, cell morphology, gene expression, stress resistance and ageing. Here, we present our studies on the mtDNA copy number in <i>Saccharomyces cerevisiae</i> chromatin mutants and investigate the mitochondrial membrane potential throughout their lifespan. The mutants are <i>arp4</i> (with a point mutation in the <i>ARP4</i> gene, coding for actin-related protein 4—Arp4p), <i>hho1Δ</i> (lacking the <i>HHO1</i> gene, coding for the linker histone H1), and the double mutant <i>arp4 hho1Δ</i> cells with the two mutations. Our findings showed that the three chromatin mutants acquired strain-specific changes in the mtDNA copy number. Furthermore, we detected the disrupted mitochondrial membrane potential in their chronological lifespan. In addition, the expression of nuclear genes responsible for regulating mitochondria biogenesis and turnover was changed. The most pronounced were the alterations found in the double mutant <i>arp4 hho1Δ</i> strain, which appeared as the only petite colony-forming mutant, unable to grow on respiratory substrates and with partial depletion of the mitochondrial genome. The results suggest that in the studied chromatin mutants, <i>hho1Δ</i>, <i>arp4</i> and <i>arp4 hho1Δ</i>, the nucleus-mitochondria communication was disrupted, leading to impaired mitochondrial function and premature ageing phenotype in these mutants, especially in the double mutant. |
| first_indexed | 2024-03-11T06:20:36Z |
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| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-11T06:20:36Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-e630bb19a86d43c487c3391b1326ce322023-11-17T12:00:02ZengMDPI AGJournal of Fungi2309-608X2023-03-019332910.3390/jof9030329Yeast Chromatin Mutants Reveal Altered mtDNA Copy Number and Impaired Mitochondrial Membrane PotentialDessislava Staneva0Bela Vasileva1Petar Podlesniy2George Miloshev3Milena Georgieva4Laboratory of Molecular Genetics, Epigenetics and Longevity, Institute of Molecular Biology “RoumenTsanev”, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaLaboratory of Molecular Genetics, Epigenetics and Longevity, Institute of Molecular Biology “RoumenTsanev”, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaCiberNed (Centro Investigacion Biomedica en Red Enfermedades Neurodegenerativas), 28029 Barcelona, SpainLaboratory of Molecular Genetics, Epigenetics and Longevity, Institute of Molecular Biology “RoumenTsanev”, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaLaboratory of Molecular Genetics, Epigenetics and Longevity, Institute of Molecular Biology “RoumenTsanev”, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaMitochondria are multifunctional, dynamic organelles important for stress response, cell longevity, ageing and death. Although the mitochondrion has its genome, nuclear-encoded proteins are essential in regulating mitochondria biogenesis, morphology, dynamics and function. Moreover, chromatin structure and epigenetic mechanisms govern the accessibility to DNA and control gene transcription, indirectly influencing nucleo-mitochondrial communications. Thus, they exert crucial functions in maintaining proper chromatin structure, cell morphology, gene expression, stress resistance and ageing. Here, we present our studies on the mtDNA copy number in <i>Saccharomyces cerevisiae</i> chromatin mutants and investigate the mitochondrial membrane potential throughout their lifespan. The mutants are <i>arp4</i> (with a point mutation in the <i>ARP4</i> gene, coding for actin-related protein 4—Arp4p), <i>hho1Δ</i> (lacking the <i>HHO1</i> gene, coding for the linker histone H1), and the double mutant <i>arp4 hho1Δ</i> cells with the two mutations. Our findings showed that the three chromatin mutants acquired strain-specific changes in the mtDNA copy number. Furthermore, we detected the disrupted mitochondrial membrane potential in their chronological lifespan. In addition, the expression of nuclear genes responsible for regulating mitochondria biogenesis and turnover was changed. The most pronounced were the alterations found in the double mutant <i>arp4 hho1Δ</i> strain, which appeared as the only petite colony-forming mutant, unable to grow on respiratory substrates and with partial depletion of the mitochondrial genome. The results suggest that in the studied chromatin mutants, <i>hho1Δ</i>, <i>arp4</i> and <i>arp4 hho1Δ</i>, the nucleus-mitochondria communication was disrupted, leading to impaired mitochondrial function and premature ageing phenotype in these mutants, especially in the double mutant.https://www.mdpi.com/2309-608X/9/3/329chromatin<i>hho1</i><i>Δ</i><i>arp4</i>ageingmitochondriarho- phenotype |
| spellingShingle | Dessislava Staneva Bela Vasileva Petar Podlesniy George Miloshev Milena Georgieva Yeast Chromatin Mutants Reveal Altered mtDNA Copy Number and Impaired Mitochondrial Membrane Potential Journal of Fungi chromatin <i>hho1</i><i>Δ</i> <i>arp4</i> ageing mitochondria rho- phenotype |
| title | Yeast Chromatin Mutants Reveal Altered mtDNA Copy Number and Impaired Mitochondrial Membrane Potential |
| title_full | Yeast Chromatin Mutants Reveal Altered mtDNA Copy Number and Impaired Mitochondrial Membrane Potential |
| title_fullStr | Yeast Chromatin Mutants Reveal Altered mtDNA Copy Number and Impaired Mitochondrial Membrane Potential |
| title_full_unstemmed | Yeast Chromatin Mutants Reveal Altered mtDNA Copy Number and Impaired Mitochondrial Membrane Potential |
| title_short | Yeast Chromatin Mutants Reveal Altered mtDNA Copy Number and Impaired Mitochondrial Membrane Potential |
| title_sort | yeast chromatin mutants reveal altered mtdna copy number and impaired mitochondrial membrane potential |
| topic | chromatin <i>hho1</i><i>Δ</i> <i>arp4</i> ageing mitochondria rho- phenotype |
| url | https://www.mdpi.com/2309-608X/9/3/329 |
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