Applicability of Yeast Genetics to Neurologic Disease

Walberg, Mark W.

doi:10.1001/archneur.57.8.1129

Cited by 18 publications

(16 citation statements)

References 18 publications

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“…Proper biogenesis and inheritance of mitochondria is critical for eukaryotes as 1 in 5,000 humans suffers from a mitochondrial disease [4]. Saccharomyces has proven to be an invaluable system for studying a variety of human diseases [5],[6], including cancer [7], neurologic disorders [8], and mitochondrial diseases [9]–[11]. Yeast is a particularly attractive model system for studying mitochondrial biology due to its ability to survive without respiration, permitting the characterization of mutants that impair mitochondrial function.…”

Section: Introductionmentioning

confidence: 99%

Computationally Driven, Quantitative Experiments Discover Genes Required for Mitochondrial Biogenesis

et al. 2009

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Mitochondria are central to many cellular processes including respiration, ion homeostasis, and apoptosis. Using computational predictions combined with traditional quantitative experiments, we have identified 100 proteins whose deficiency alters mitochondrial biogenesis and inheritance in Saccharomyces cerevisiae. In addition, we used computational predictions to perform targeted double-mutant analysis detecting another nine genes with synthetic defects in mitochondrial biogenesis. This represents an increase of about 25% over previously known participants. Nearly half of these newly characterized proteins are conserved in mammals, including several orthologs known to be involved in human disease. Mutations in many of these genes demonstrate statistically significant mitochondrial transmission phenotypes more subtle than could be detected by traditional genetic screens or high-throughput techniques, and 47 have not been previously localized to mitochondria. We further characterized a subset of these genes using growth profiling and dual immunofluorescence, which identified genes specifically required for aerobic respiration and an uncharacterized cytoplasmic protein required for normal mitochondrial motility. Our results demonstrate that by leveraging computational analysis to direct quantitative experimental assays, we have characterized mutants with subtle mitochondrial defects whose phenotypes were undetected by high-throughput methods.

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Section: Introductionmentioning

confidence: 99%

Computationally Driven, Quantitative Experiments Discover Genes Required for Mitochondrial Biogenesis

et al. 2009

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“…It has provided the basis for much of our understanding of the genetics, biochemistry, physiology and structure of eukaryotic cells (Botstein et al, 1997;Dolinski and Botstein, 2007;Kane and Roth, 1974;Lee and Young, 2000;Mackay, 2001;Moler et al, 2000;Myers and Kornberg, 2000;Nyberg et al, 2002;Sherman, 2005;Walberg, 2000;Wickner and Haas, 2000). The simplicity and speed of its life cycle and the facility with which it can be manipulated in the laboratory have made it the organism of choice for technologies ranging from yeast artificial chromosomes (YACs; Burke et al, 1987) to twohybrid selections (Fields and Song, 1989), microarrays (Brown and Botstein, 1999) and proteomics (Hodges et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

A new yeast genetic resource for analysis and breeding

Timberlake¹,

Frizzell²,

Richards

et al. 2010

Yeast

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We made a library of Saccharomyces cerevisiae F 1 hybrids from all possible crosses of 16 wild-type strains, including two common laboratory strains and two commercial winemaking varieties. Fourteen of the starting strains have been sequenced. Thus, the sequences of both genomes are known in 182 novel hybrids, and the sequence of one genome is known in 56. All tested strains sporulated. Fertilities were in the range 0-100%. Hybrids showed no more variation than parental strains for ethanol production, ethanol tolerance or growth at temperature extremes, but some F 1 s appeared to display hybrid vigour (heterosis). We tested four tetrads from one hybrid for their ability to grow at low temperature or in the presence of an inhibitory concentration of ethanol. Only one F 2 was as tolerant as the most tolerant F 0 parent. A few showed intermediate tolerance, but most were less tolerant than either parent or the F 1 hybrid, consistent with uncoupling of genes contributing to an optimized quantitative trait. The diversity and structure of the library should make it useful for analysis of genetic interactions among diverse strains, quantitative inheritance and heterosis, and for breeding.

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“…Exploitation of yeast as a model system has laid the groundwork for subsequent work on a wide range of human disease genes related to mitochondrial disorders [183, 184], metabolic disorders [185–187], aging [188, 189], neurodegeneration [190, 191], and cancer [192], often leading to major new lines of research. Perhaps the most unexpected application of yeast genetics is in the study of neurodegeneration, where yeast have contributed importantly to our understanding of the mechanisms of protein misfolding and aggregation common to Huntington’s disease (HD), Parkinson’s disease (PD), and Alzheimer’s disease (AD) [193–195].…”

Section: Non-mammalian Models Of Human Diseasesmentioning

confidence: 99%

Mitochondrial involvement in cell death of non-mammalian eukaryotes

Abdelwahid

Rolland

Teng

et al. 2011

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Although mitochondria are essential organelles for long-term survival of eukaryotic cells, recent discoveries in biochemistry and genetics have advanced our understanding of the requirements for mitochondria in cell death. Much of what we understand about cell death is based on the identification of conserved cell death genes in Drosophila melanogaster and Caenorhabditis elegans. However, the role of mitochondria in cell death in these models has been much less clear. Considering the active role that mitochondria play in apoptosis in mammalian cells, the mitochondrial contribution to cell death in non-mammalian systems has been an area of active investigation. In this article, we review the current research on this topic in three non-mammalian models, C. elegans, Drosophila and Saccharomyces cerevisiae. In addition, we discuss how non-mammalian models have provided important insight into the mechanisms of human disease as they relate to the mitochondrial pathway of cell death. The unique perspective derived from each of these model systems provides a more complete understanding of mitochondria in programmed cell death.

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Applicability of Yeast Genetics to Neurologic Disease

Cited by 18 publications

References 18 publications

Computationally Driven, Quantitative Experiments Discover Genes Required for Mitochondrial Biogenesis

Computationally Driven, Quantitative Experiments Discover Genes Required for Mitochondrial Biogenesis

A new yeast genetic resource for analysis and breeding

Mitochondrial involvement in cell death of non-mammalian eukaryotes

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