A vital function for mitochondrial DNA in the petite-negative yeastKluyveromyces lactis

Clark-Walker, G. D.; Chen, X. J.

doi:10.1007/bf02173982

Cited by 12 publications

(5 citation statements)

References 23 publications

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“…This is in contrast to S. cerevisiae , which is petite positive as deletions in the mitochondrial DNA are not lethal. Mutations in K. lactis were identified that convert the cells from petite negative to petite positive and the complementation group was named m itochondrial g enome i ntegrity ( mgi ) 113 114 115 116 117 118 . Surprisingly, the mgi mutations mapped in the genes encoding α-, β-, and γ-subunits of the mitochondrial ATP synthase.…”

Section: Structure and Organization Of The F 1 F mentioning

confidence: 99%

Understanding structure, function, and mutations in the mitochondrial ATP synthase

Pagadala

Mueller

2015

MIC

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The mitochondrial ATP synthase is a multimeric enzyme complex with an overall molecular weight of about 600,000 Da. The ATP synthase is a molecular motor composed of two separable parts: F1 and Fo. The F1 portion contains the catalytic sites for ATP synthesis and protrudes into the mitochondrial matrix. Fo forms a proton turbine that is embedded in the inner membrane and connected to the rotor of F1. The flux of protons flowing down a potential gradient powers the rotation of the rotor driving the synthesis of ATP. Thus, the flow of protons though Fo is coupled to the synthesis of ATP. This review will discuss the structure/function relationship in the ATP synthase as determined by biochemical, crystallographic, and genetic studies. An emphasis will be placed on linking the structure/function relationship with understanding how disease causing mutations or putative single nucleotide polymorphisms (SNPs) in genes encoding the subunits of the ATP synthase, will affect the function of the enzyme and the health of the individual. The review will start by summarizing the current understanding of the subunit composition of the enzyme and the role of the subunits followed by a discussion on known mutations and their effect on the activity of the ATP synthase. The review will conclude with a summary of mutations in genes encoding subunits of the ATP synthase that are known to be responsible for human disease, and a brief discussion on SNPs.

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Section: Structure and Organization Of The F 1 F mentioning

confidence: 99%

Understanding structure, function, and mutations in the mitochondrial ATP synthase

Pagadala

Mueller

2015

MIC

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“…lactis and S . pombe MGM101 homologues have been identified ( Chen et al, 1993 ; Clark-Walker and Chen, 1996 ; see Fig. 1 ).…”

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confidence: 99%

Mgm101p Is a Novel Component of the Mitochondrial Nucleoid That Binds DNA and Is Required for the Repair of Oxidatively Damaged Mitochondrial DNA

Meeusen

Tieu

Wong

et al. 1999

The Journal of Cell Biology

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Maintenance of mitochondrial DNA (mtDNA) during cell division is required for progeny to be respiratory competent. Maintenance involves the replication, repair, assembly, segregation, and partitioning of the mitochondrial nucleoid. MGM101 has been identified as a gene essential for mtDNA maintenance in S. cerevisiae, but its role is unknown. Using liquid chromatography coupled with tandem mass spectrometry, we identified Mgm101p as a component of highly enriched nucleoids, suggesting that it plays a nucleoid-specific role in maintenance. Subcellular fractionation, indirect immunofluorescence and GFP tagging show that Mgm101p is exclusively associated with the mitochondrial nucleoid structure in cells. Furthermore, DNA affinity chromatography of nucleoid extracts indicates that Mgm101p binds to DNA, suggesting that its nucleoid localization is in part due to this activity. Phenotypic analysis of cells containing a temperature sensitive mgm101 allele suggests that Mgm101p is not involved in mtDNA packaging, segregation, partitioning or required for ongoing mtDNA replication. We examined Mgm101p's role in mtDNA repair. As compared with wild-type cells, mgm101 cells were more sensitive to mtDNA damage induced by UV irradiation and were hypersensitive to mtDNA damage induced by gamma rays and H2O2 treatment. Thus, we propose that Mgm101p performs an essential function in the repair of oxidatively damaged mtDNA that is required for the maintenance of the mitochondrial genome.

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“…In addition to the loss of or mutations in mtDNA (i.e., cytoplasmic petite), mutations occurring in the nuclear genome can also generate the petite phenotype (i.e., nuclear petite) if the nuclear genes required for respiratory growth or encoding mitochondrial proteins are disrupted. Moreover, mtDNA loss is lethal in the wildtype yeast species Kluyveromyces lactis (petite-negative) [ 10 ]. Thus, the petite phenotype reflects stresses that cells have to deal with when respiratory dysfunction occurs.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous Mutation Rates and Spectra of Respiratory-Deficient Yeast

Wang

Liti

et al. 2023

Biomolecules

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The yeast petite mutant was first discovered in the yeast Saccharomyces cerevisiae, which shows growth stress due to defects in genes encoding the respiratory chain. In a previous study, we described that deletion of the nuclear-encoded gene MRPL25 leads to mitochondrial genome (mtDNA) loss and the petite phenotype, which can be rescued by acquiring ATP3 mutations. The mrpl25Δ strain showed an elevated SNV (single nucleotide variant) rate, suggesting genome instability occurred during the crisis of mtDNA loss. However, the genome-wide mutation landscape and mutational signatures of mitochondrial dysfunction are unknown. In this study we profiled the mutation spectra in yeast strains with the genotype combination of MRPL25 and ATP3 in their wildtype and mutated status, along with the wildtype and cytoplasmic petite rho0 strains as controls. In addition to the previously described elevated SNV rate, we found the INDEL (insertion/deletion) rate also increased in the mrpl25Δ strain, reinforcing the occurrence of genome instability. Notably, although both are petites, the mrpl25Δ and rho0 strains exhibited different INDEL rates and transition/transversion ratios, suggesting differences in the mutational signatures underlying these two types of petites. Interestingly, the petite-related mutagenesis effect disappeared when ATP3 suppressor mutations were acquired, suggesting a cost-effective mechanism for restoring both fitness and genome stability. Taken together, we present an unbiased genome-wide characterization of the mutation rates and spectra of yeast strains with respiratory deficiency, which provides valuable insights into the impact of respiratory deficiency on genome instability.

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A vital function for mitochondrial DNA in the petite-negative yeastKluyveromyces lactis

Cited by 12 publications

References 23 publications

Understanding structure, function, and mutations in the mitochondrial ATP synthase

Understanding structure, function, and mutations in the mitochondrial ATP synthase

Mgm101p Is a Novel Component of the Mitochondrial Nucleoid That Binds DNA and Is Required for the Repair of Oxidatively Damaged Mitochondrial DNA

Spontaneous Mutation Rates and Spectra of Respiratory-Deficient Yeast

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