Staneva Dessislava, Vasileva Bela, Podlesniy Petar, Miloshev George, Georgieva Milena
Laboratory of Molecular Genetics, Epigenetics and Longevity, Institute of Molecular Biology "RoumenTsanev", Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
CiberNed (Centro Investigacion Biomedica en Red Enfermedades Neurodegenerativas), 28029 Barcelona, Spain.
J Fungi (Basel). 2023 Mar 7;9(3):329. doi: 10.3390/jof9030329.
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 chromatin mutants and investigate the mitochondrial membrane potential throughout their lifespan. The mutants are (with a point mutation in the gene, coding for actin-related protein 4-Arp4p), (lacking the gene, coding for the linker histone H1), and the double mutant 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 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, , and , the nucleus-mitochondria communication was disrupted, leading to impaired mitochondrial function and premature ageing phenotype in these mutants, especially in the double mutant.
线粒体是多功能的动态细胞器，对应激反应、细胞寿命、衰老和死亡至关重要。尽管线粒体有其自身的基因组，但核编码蛋白对于调节线粒体的生物发生、形态、动态变化和功能必不可少。此外，染色质结构和表观遗传机制决定了DNA的可及性并控制基因转录，间接影响核-线粒体通讯。因此，它们在维持适当的染色质结构、细胞形态、基因表达、抗逆性和衰老方面发挥着关键作用。在此，我们展示了对染色质突变体中线粒体DNA拷贝数的研究，并在其整个生命周期中研究线粒体膜电位。这些突变体包括（在编码肌动蛋白相关蛋白4-Arp4p的基因中有一个点突变）、（缺乏编码连接组蛋白H1的基因）以及具有这两种突变的双突变细胞。我们的研究结果表明，这三种染色质突变体在mtDNA拷贝数上出现了菌株特异性变化。此外，我们在它们的时序寿命中检测到线粒体膜电位的破坏。此外，负责调节线粒体生物发生和周转的核基因表达也发生了变化。最显著的变化出现在双突变菌株中，它是唯一形成小菌落的突变体，无法在呼吸底物上生长，线粒体基因组部分缺失。结果表明，在所研究的染色质突变体、和中，核-线粒体通讯被破坏，导致这些突变体中线粒体功能受损和早衰表型，尤其是在双突变体中。
