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14 pages, 2099 KiB

Open AccessArticle

Eukaryotic Elongation Factor 3 Protects Saccharomyces cerevisiae Yeast from Oxidative Stress

by Karolina Gościńska, Somayeh Shahmoradi Ghahe, Sara Domogała and Ulrike Topf

Genes 2020, 11(12), 1432; https://doi.org/10.3390/genes11121432 - 28 Nov 2020

Cited by 8 | Viewed by 3650

Abstract

Translation is a core process of cellular protein homeostasis and, thus, needs to be tightly regulated. The production of newly synthesized proteins adapts to the current needs of the cell, including the response to conditions of oxidative stress. Overall protein synthesis decreases upon [...] Read more.

Translation is a core process of cellular protein homeostasis and, thus, needs to be tightly regulated. The production of newly synthesized proteins adapts to the current needs of the cell, including the response to conditions of oxidative stress. Overall protein synthesis decreases upon oxidative stress. However, the selective production of proteins is initiated to help neutralize stress conditions. In contrast to higher eukaryotes, fungi require three translation elongation factors, eEF1, eEF2, and eEF3, for protein synthesis. eEF1 and eEF2 are evolutionarily conserved, but they alone are insufficient for the translation elongation process. eEF3 is encoded by two paralogous genes, YEF3 and HEF3. However, only YEF3 is essential in yeast, whereas the function of HEF3 remains unknown. To elucidate the cellular function of Hef3p, we used cells that were depleted of HEF3 and treated with H₂O₂ and analyzed the growth of yeast, global protein production, and protein levels. We found that HEF3 is necessary to withstand oxidative stress conditions, suggesting that Hef3p is involved in the selective production of proteins that are necessary for defense against reactive oxygen species. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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18 pages, 1060 KiB

Open AccessArticle

Slow Adaptive Response of Budding Yeast Cells to Stable Conditions of Continuous Culture Can Occur without Genome Modifications

by Joanna Klim, Urszula Zielenkiewicz, Anna Kurlandzka, Szymon Kaczanowski and Marek Skoneczny

Genes 2020, 11(12), 1419; https://doi.org/10.3390/genes11121419 - 27 Nov 2020

Cited by 1 | Viewed by 2601

Abstract

Continuous cultures assure the invariability of environmental conditions and the metabolic state of cultured microorganisms, whereas batch-cultured cells undergo constant changes in nutrients availability. For that reason, continuous culture is sometimes employed in the whole transcriptome, whole proteome, or whole metabolome studies. However, [...] Read more.

Continuous cultures assure the invariability of environmental conditions and the metabolic state of cultured microorganisms, whereas batch-cultured cells undergo constant changes in nutrients availability. For that reason, continuous culture is sometimes employed in the whole transcriptome, whole proteome, or whole metabolome studies. However, the typical method for establishing uniform growth of a cell population, i.e., by limited chemostat, results in the enrichment of the cell population gene pool with mutations adaptive for starvation conditions. These adaptive changes can skew the results of large-scale studies. It is commonly assumed that these adaptations reflect changes in the genome, and this assumption has been confirmed experimentally in rare cases. Here we show that in a population of budding yeast cells grown for over 200 generations in continuous culture in non-limiting minimal medium and therefore not subject to selection pressure, remodeling of transcriptome occurs, but not as a result of the accumulation of adaptive mutations. The observed changes indicate a shift in the metabolic balance towards catabolism, a decrease in ribosome biogenesis, a decrease in general stress alertness, reorganization of the cell wall, and transactions occurring at the cell periphery. These adaptive changes signify the acquisition of a new lifestyle in a stable nonstressful environment. The absence of underlying adaptive mutations suggests these changes may be regulated by another mechanism. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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13 pages, 1400 KiB

Open AccessArticle

Dissecting the Genetic Regulation of Yeast Growth Plasticity in Response to Environmental Changes

by Yanjun Zan and Örjan Carlborg

Genes 2020, 11(11), 1279; https://doi.org/10.3390/genes11111279 - 29 Oct 2020

Cited by 5 | Viewed by 2699

Abstract

Variable individual responses to environmental changes, such as phenotype plasticity, are heritable, with some genotypes being robust and others plastic. This variation for plasticity contributes to variance in complex traits as genotype-by-environment interactions (G × E). However, the genetic basis of this variability [...] Read more.

Variable individual responses to environmental changes, such as phenotype plasticity, are heritable, with some genotypes being robust and others plastic. This variation for plasticity contributes to variance in complex traits as genotype-by-environment interactions (G × E). However, the genetic basis of this variability in responses to the same external stimuli is still largely unknown. In an earlier study of a large haploid segregant yeast population, genotype-by-genotype-by-environment interactions were found to make important contributions to the release of genetic variation in growth responses to alterations of the growth medium. Here, we explore the genetic basis for heritable variation of different measures of phenotype plasticity in the same dataset. We found that the central loci in the environmentally dependent epistatic networks were associated with overall measures of plasticity, while the specific measures of plasticity identified a more diverse set of loci. Based on this, a rapid one-dimensional genome-wide association (GWA) approach to overall plasticity is proposed as a strategy to efficiently identify key epistatic loci contributing to the phenotype plasticity. The study thus provided both analytical strategies and a deeper understanding of the complex genetic regulation of phenotype plasticity in yeast growth. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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26 pages, 7594 KiB

Open AccessFeature PaperArticle

Synthetic Pesticides Used in Agricultural Production Promote Genetic Instability and Metabolic Variability in Candida spp.

by Leszek Potocki, Aleksandra Baran, Bernadetta Oklejewicz, Ewa Szpyrka, Magdalena Podbielska and Viera Schwarzbacherová

Genes 2020, 11(8), 848; https://doi.org/10.3390/genes11080848 - 24 Jul 2020

Cited by 6 | Viewed by 3281

Abstract

The effects of triazole fungicide Tango^® (epoxiconazole) and two neonicotinoid insecticide formulations Mospilan^® (acetamiprid) and Calypso^® (thiacloprid) were investigated in Candida albicans and three non-albicans species Candida pulcherrima, Candida glabrata and Candida tropicalis to assess the range of morphological, metabolic [...] Read more.

The effects of triazole fungicide Tango^® (epoxiconazole) and two neonicotinoid insecticide formulations Mospilan^® (acetamiprid) and Calypso^® (thiacloprid) were investigated in Candida albicans and three non-albicans species Candida pulcherrima, Candida glabrata and Candida tropicalis to assess the range of morphological, metabolic and genetic changes after their exposure to pesticides. Moreover, the bioavailability of pesticides, which gives us information about their metabolization was assessed using gas chromatography-mass spectrophotometry (GC-MS). The tested pesticides caused differences between the cells of the same species in the studied populations in response to ROS accumulation, the level of DNA damage, changes in fatty acids (FAs) and phospholipid profiles, change in the percentage of unsaturated to saturated FAs or the ability to biofilm. In addition, for the first time, the effect of tested neonicotinoid insecticides on the change of metabolic profile of colony cells during aging was demonstrated. Our data suggest that widely used pesticides, including insecticides, may increase cellular diversity in the Candida species population-known as clonal heterogeneity-and thus play an important role in acquiring resistance to antifungal agents. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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17 pages, 3043 KiB

Open AccessArticle

Flavonoids as Potential Drugs for VPS13-Dependent Rare Neurodegenerative Diseases

by Piotr Soczewka, Krzysztof Flis, Déborah Tribouillard-Tanvier, Jean-Paul di Rago, Cláudia N. Santos, Regina Menezes, Joanna Kaminska and Teresa Zoladek

Genes 2020, 11(7), 828; https://doi.org/10.3390/genes11070828 - 21 Jul 2020

Cited by 12 | Viewed by 3498

Abstract

Several rare neurodegenerative diseases, including chorea acanthocytosis, are caused by mutations in the VPS13A–D genes. Only symptomatic treatments for these diseases are available. Saccharomyces cerevisiae contains a unique VPS13 gene and the yeast vps13Δ mutant has been proven as a [...] Read more.

Several rare neurodegenerative diseases, including chorea acanthocytosis, are caused by mutations in the VPS13A–D genes. Only symptomatic treatments for these diseases are available. Saccharomyces cerevisiae contains a unique VPS13 gene and the yeast vps13Δ mutant has been proven as a suitable model for drug tests. A library of drugs and an in-house library of natural compounds and their derivatives were screened for molecules preventing the growth defect of vps13Δ cells on medium with sodium dodecyl sulfate (SDS). Seven polyphenols, including the iron-binding flavone luteolin, were identified. The structure–activity relationship and molecular mechanisms underlying the action of luteolin were characterized. The FET4 gene, which encodes an iron transporter, was found to be a multicopy suppressor of vps13Δ, pointing out the importance of iron in response to SDS stress. The growth defect of vps13Δ in SDS-supplemented medium was also alleviated by the addition of iron salts. Suppression did not involve cell antioxidant responses, as chemical antioxidants were not active. Our findings support that luteolin and iron may target the same cellular process, possibly the synthesis of sphingolipids. Unveiling the mechanisms of action of chemical and genetic suppressors of vps13Δ may help to better understand VPS13A–D-dependent pathogenesis and to develop novel therapeutic strategies. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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19 pages, 2314 KiB

Open AccessArticle

Linkage between Carbon Metabolism, Redox Status and Cellular Physiology in the Yeast Saccharomyces cerevisiae Devoid of SOD1 or SOD2 Gene

by Roman Maslanka, Renata Zadrag-Tecza and Magdalena Kwolek-Mirek

Genes 2020, 11(7), 780; https://doi.org/10.3390/genes11070780 - 11 Jul 2020

Cited by 24 | Viewed by 3909

Abstract

Saccharomyces cerevisiae yeast cells may generate energy both by fermentation and aerobic respiration, which are dependent on the type and availability of carbon sources. Cells adapt to changes in nutrient availability, which entails the specific costs and benefits of different types of metabolism [...] Read more.

Saccharomyces cerevisiae yeast cells may generate energy both by fermentation and aerobic respiration, which are dependent on the type and availability of carbon sources. Cells adapt to changes in nutrient availability, which entails the specific costs and benefits of different types of metabolism but also may cause alteration in redox homeostasis, both by changes in reactive oxygen species (ROS) and in cellular reductant molecules contents. In this study, yeast cells devoid of the SOD1 or SOD2 gene and fermentative or respiratory conditions were used to unravel the connection between the type of metabolism and redox status of cells and also how this affects selected parameters of cellular physiology. The performed analysis provides an argument that the source of ROS depends on the type of metabolism and non-mitochondrial sources are an important pool of ROS in yeast cells, especially under fermentative metabolism. There is a strict interconnection between carbon metabolism and redox status, which in turn has an influence on the physiological efficiency of the cells. Furthermore, pyridine nucleotide cofactors play an important role in these relationships. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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15 pages, 3258 KiB

Open AccessArticle

Identification of Genes Encoding CENP-A and Heterochromatin Protein 1 of Lipomyces starkeyi and Functional Analysis Using Schizosaccharomyces pombe

by Yuko Takayama

Genes 2020, 11(7), 769; https://doi.org/10.3390/genes11070769 - 8 Jul 2020

Cited by 1 | Viewed by 3061

Abstract

Centromeres function as a platform for the assembly of multiple kinetochore proteins and are essential for chromosome segregation. An active centromere is characterized by the presence of a centromere-specific histone H3 variant, CENP-A. Faithful centromeric localization of CENP-A is supported by heterochromatin in [...] Read more.

Centromeres function as a platform for the assembly of multiple kinetochore proteins and are essential for chromosome segregation. An active centromere is characterized by the presence of a centromere-specific histone H3 variant, CENP-A. Faithful centromeric localization of CENP-A is supported by heterochromatin in almost all eukaryotes; however, heterochromatin proteins have been lost in most Saccharomycotina. Here, identification of CENP-A (CENP-A^L.s.) and heterochromatin protein 1 (Lsw1) in a Saccharomycotina species, the oleaginous yeast Lipomyces starkeyi, is reported. To determine if these proteins are functional, the proteins in S. pombe, a species widely used to study centromeres, were ectopically expressed. CENP-A^L.s. localizes to centromeres and can be replaced with S. pombe CENP-A, indicating that CENP-A^L.s. is a functional centromere-specific protein. Lsw1 binds at heterochromatin regions, and chromatin binding is dependent on methylation of histone H3 at lysine 9. In other species, self-interaction of heterochromatin protein 1 is thought to cause folding of chromatin, triggering transcription repression and heterochromatin formation. Consistent with this, it was found that Lsw1 can self-interact. L. starkeyi chromatin contains the methylation of histone H3 at lysine 9. These results indicated that L. starkeyi has a primitive heterochromatin structure and is an attractive model for analysis of centromere heterochromatin evolution. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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15 pages, 1848 KiB

Open AccessCommunication

Long-Term Adaption to High Osmotic Stress as a Tool for Improving Enological Characteristics in Industrial Wine Yeast

by Gabriela Betlej, Ewelina Bator, Bernadetta Oklejewicz, Leszek Potocki, Anna Górka, Magdalena Slowik-Borowiec, Wojciech Czarny, Wojciech Domka and Aleksandra Kwiatkowska

Genes 2020, 11(5), 576; https://doi.org/10.3390/genes11050576 - 20 May 2020

Cited by 16 | Viewed by 4169

Abstract

Industrial wine yeasts owe their adaptability in constantly changing environments to a long evolutionary history that combines naturally occurring evolutionary events with human-enforced domestication. Among the many stressors associated with winemaking processes that have potentially detrimental impacts on yeast viability, growth, and fermentation [...] Read more.

Industrial wine yeasts owe their adaptability in constantly changing environments to a long evolutionary history that combines naturally occurring evolutionary events with human-enforced domestication. Among the many stressors associated with winemaking processes that have potentially detrimental impacts on yeast viability, growth, and fermentation performance are hyperosmolarity, high glucose concentrations at the beginning of fermentation, followed by the depletion of nutrients at the end of this process. Therefore, in this study, we subjected three widely used industrial wine yeasts to adaptive laboratory evolution under potassium chloride (KCl)-induced osmotic stress. At the end of the evolutionary experiment, we evaluated the tolerance to high osmotic stress of the evolved strains. All of the analyzed strains improved their fitness under high osmotic stress without worsening their economic characteristics, such as growth rate and viability. The evolved derivatives of two strains also gained the ability to accumulate glycogen, a readily mobilized storage form of glucose conferring enhanced viability and vitality of cells during prolonged nutrient deprivation. Moreover, laboratory-scale fermentation in grape juice showed that some of the KCl-evolved strains significantly enhanced glycerol synthesis and production of resveratrol-enriched wines, which in turn greatly improved the wine sensory profile. Altogether, these findings showed that long-term adaptations to osmotic stress can be an attractive approach to develop industrial yeasts. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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14 pages, 3243 KiB

Open AccessArticle

Pathogenic Effect of GDAP1 Gene Mutations in a Yeast Model

by Weronika Rzepnikowska, Joanna Kaminska, Dagmara Kabzińska and Andrzej Kochański

Genes 2020, 11(3), 310; https://doi.org/10.3390/genes11030310 - 14 Mar 2020

Cited by 10 | Viewed by 3320

Abstract

The question of whether a newly identified sequence variant is truly a causative mutation is a central problem of modern clinical genetics. In the current era of massive sequencing, there is an urgent need to develop new tools for assessing the pathogenic effect [...] Read more.

The question of whether a newly identified sequence variant is truly a causative mutation is a central problem of modern clinical genetics. In the current era of massive sequencing, there is an urgent need to develop new tools for assessing the pathogenic effect of new sequence variants. In Charcot-Marie-Tooth disorders (CMT) with their extreme genetic heterogeneity and relatively homogenous clinical presentation, addressing the pathogenic effect of rare sequence variants within 80 CMT genes is extremely challenging. The presence of multiple rare sequence variants within a single CMT-affected patient makes selection for the strongest one, the truly causative mutation, a challenging issue. In the present study we propose a new yeast-based model to evaluate the pathogenic effect of rare sequence variants found within the one of the CMT-associated genes, GDAP1. In our approach, the wild-type and pathogenic variants of human GDAP1 gene were expressed in yeast. Then, a growth rate and mitochondrial morphology and function of GDAP1-expressing strains were studied. Also, the mutant GDAP1 proteins localization and functionality were assessed in yeast. We have shown, that GDAP1 was not only stably expressed but also functional in yeast cell, as it influenced morphology and function of mitochondria and altered the growth of a mutant yeast strain. What is more, the various GDAP1 pathogenic sequence variants caused the specific for them effect in the tests we performed. Thus, the proposed model is suitable for validating the pathogenic effect of known GDAP1 mutations and may be used for testing of unknown sequence variants found in CMT patients. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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Review

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20 pages, 1107 KiB

Open AccessReview

Metabolic Engineering of Wine Strains of Saccharomyces cerevisiae

by Mikhail A. Eldarov and Andrey V. Mardanov

Genes 2020, 11(9), 964; https://doi.org/10.3390/genes11090964 - 20 Aug 2020

Cited by 14 | Viewed by 5321

Abstract

Modern industrial winemaking is based on the use of starter cultures of specialized wine strains of Saccharomyces cerevisiae yeast. Commercial wine strains have a number of advantages over natural isolates, and it is their use that guarantees the stability and reproducibility of industrial [...] Read more.

Modern industrial winemaking is based on the use of starter cultures of specialized wine strains of Saccharomyces cerevisiae yeast. Commercial wine strains have a number of advantages over natural isolates, and it is their use that guarantees the stability and reproducibility of industrial winemaking technologies. For the highly competitive wine market with new demands for improved wine quality, it has become increasingly critical to develop new wine strains and winemaking technologies. Novel opportunities for precise wine strain engineering based on detailed knowledge of the molecular nature of a particular trait or phenotype have recently emerged due to the rapid progress in genomic and “postgenomic” studies with wine yeast strains. The review summarizes the current achievements of the metabolic engineering of wine yeast, the results of recent studies and the prospects for the application of genomic editing technologies for improving wine S. cerevisiae strains. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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11 pages, 1068 KiB

Open AccessReview

New Perspectives on SNARE Function in the Yeast Minimal Endomembrane System

by James H. Grissom, Verónica A. Segarra and Richard J. Chi

Genes 2020, 11(8), 899; https://doi.org/10.3390/genes11080899 - 6 Aug 2020

Cited by 12 | Viewed by 4745

Abstract

Saccharomyces cerevisiae is one of the best model organisms for the study of endocytic membrane trafficking. While studies in mammalian cells have characterized the temporal and morphological features of the endocytic pathway, studies in budding yeast have led the way in the analysis [...] Read more.

Saccharomyces cerevisiae is one of the best model organisms for the study of endocytic membrane trafficking. While studies in mammalian cells have characterized the temporal and morphological features of the endocytic pathway, studies in budding yeast have led the way in the analysis of the endosomal trafficking machinery components and their functions. Eukaryotic endomembrane systems were thought to be highly conserved from yeast to mammals, with the fusion of plasma membrane-derived vesicles to the early or recycling endosome being a common feature. Upon endosome maturation, cargos are then sorted for reuse or degraded via the endo-lysosomal (endo-vacuolar in yeast) pathway. However, recent studies have shown that budding yeast has a minimal endomembrane system that is fundamentally different from that of mammalian cells, with plasma membrane-derived vesicles fusing directly to a trans-Golgi compartment which acts as an early endosome. Thus, the Golgi, rather than the endosome, acts as the primary acceptor of endocytic vesicles, sorting cargo to pre-vacuolar endosomes for degradation. The field must now integrate these new findings into a broader understanding of the endomembrane system across eukaryotes. This article synthesizes what we know about the machinery mediating endocytic membrane fusion with this new model for yeast endomembrane function. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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11 pages, 1882 KiB

Open AccessReview

Cryopreservation and the Freeze–Thaw Stress Response in Yeast

by Elizabeth Cabrera, Laylah C. Welch, Meaghan R. Robinson, Candyce M. Sturgeon, Mackenzie M. Crow and Verónica A. Segarra

Genes 2020, 11(8), 835; https://doi.org/10.3390/genes11080835 - 22 Jul 2020

Cited by 24 | Viewed by 6565

Abstract

The ability of yeast to survive freezing and thawing is most frequently considered in the context of cryopreservation, a practical step in both industrial and research applications of these organisms. However, it also relates to an evolved ability to withstand freeze–thaw stress that [...] Read more.

The ability of yeast to survive freezing and thawing is most frequently considered in the context of cryopreservation, a practical step in both industrial and research applications of these organisms. However, it also relates to an evolved ability to withstand freeze–thaw stress that is integrated with a larger network of survival responses. These responses vary between different strains and species of yeast according to the environments to which they are adapted, and the basis of this adaptation appears to be both conditioned and genetic in origin. This review article briefly touches upon common yeast cryopreservation methods and describes in detail what is known about the biochemical and genetic determinants of cell viability following freeze–thaw stress. While we focus on the budding yeast Saccharomyces cerevisiae, in which the freeze–thaw stress response is best understood, we also highlight the emerging diversity of yeast freeze–thaw responses as a manifestation of biodiversity among these organisms. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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14 pages, 834 KiB

Open AccessReview

Aspects of Multicellularity in Saccharomyces cerevisiae Yeast: A Review of Evolutionary and Physiological Mechanisms

by Monika Opalek and Dominika Wloch-Salamon

Genes 2020, 11(6), 690; https://doi.org/10.3390/genes11060690 - 24 Jun 2020

Cited by 18 | Viewed by 4598

Abstract

The evolutionary transition from single-celled to multicellular growth is a classic and intriguing problem in biology. Saccharomyces cerevisiae is a useful model to study questions regarding cell aggregation, heterogeneity and cooperation. In this review, we discuss scenarios of group formation and how this [...] Read more.

The evolutionary transition from single-celled to multicellular growth is a classic and intriguing problem in biology. Saccharomyces cerevisiae is a useful model to study questions regarding cell aggregation, heterogeneity and cooperation. In this review, we discuss scenarios of group formation and how this promotes facultative multicellularity in S. cerevisiae. We first describe proximate mechanisms leading to aggregation. These mechanisms include staying together and coming together, and can lead to group heterogeneity. Heterogeneity is promoted by nutrient limitation, structured environments and aging. We then characterize the evolutionary benefits and costs of facultative multicellularity in yeast. We summarize current knowledge and focus on the newest state-of-the-art discoveries that will fuel future research programmes aiming to understand facultative microbial multicellularity. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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14 pages, 1969 KiB

Open AccessReview

Rolling-Circle Replication in Mitochondrial DNA Inheritance: Scientific Evidence and Significance from Yeast to Human Cells

by Feng Ling and Minoru Yoshida

Genes 2020, 11(5), 514; https://doi.org/10.3390/genes11050514 - 6 May 2020

Cited by 9 | Viewed by 8270

Abstract

Studies of mitochondrial (mt)DNA replication, which forms the basis of mitochondrial inheritance, have demonstrated that a rolling-circle replication mode exists in yeasts and human cells. In yeast, rolling-circle mtDNA replication mediated by homologous recombination is the predominant pathway for replication of wild-type mtDNA. [...] Read more.

Studies of mitochondrial (mt)DNA replication, which forms the basis of mitochondrial inheritance, have demonstrated that a rolling-circle replication mode exists in yeasts and human cells. In yeast, rolling-circle mtDNA replication mediated by homologous recombination is the predominant pathway for replication of wild-type mtDNA. In human cells, reactive oxygen species (ROS) induce rolling-circle replication to produce concatemers, linear tandem multimers linked by head-to-tail unit-sized mtDNA that promote restoration of homoplasmy from heteroplasmy. The event occurs ahead of mtDNA replication mechanisms observed in mammalian cells, especially under higher ROS load, as newly synthesized mtDNA is concatemeric in hydrogen peroxide-treated human cells. Rolling-circle replication holds promise for treatment of mtDNA heteroplasmy-attributed diseases, which are regarded as incurable. This review highlights the potential therapeutic value of rolling-circle mtDNA replication. Full article

(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)

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