Mutations at different sites in members of the Gpr1/Fun34/YaaH protein family cause hypersensitivity to acetic acid in<i>Saccharomyces cerevisiae</i>as well as in<i>Yarrowia lipolytica</i>

Gentsch, Marcus; Kuschel, Margret; Schlegel, Susan; Barth, Gerold

doi:10.1111/j.1567-1364.2006.00191.x

Cited by 17 publications

(27 citation statements)

References 33 publications

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“…S4A in the supplemental material). Several fungal proteins encoded by genes in this family have been shown or suggested to mediate acetate uptake (64,65), and acetate permease activity has recently been demonstrated for the E. coli protein YaaH (66). In S. cerevisiae, both exogenous acetate and induction of the glyoxylate cycle are accompanied by strong upregulation of its GPR1/FUN30/YaaH gene (67,68).…”

Section: Resultsmentioning

confidence: 99%

The Path to Triacylglyceride Obesity in the sta6 Strain of Chlamydomonas reinhardtii

et al. 2014

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iWhen the sta6 (starch-null) strain of the green microalga Chlamydomonas reinhardtii is nitrogen starved in acetate and then "boosted" after 2 days with additional acetate, the cells become "obese" after 8 days, with triacylglyceride (TAG)-filled lipid bodies filling their cytoplasm and chloroplasts. To assess the transcriptional correlates of this response, the sta6 strain and the starch-forming cw15 strain were subjected to RNA-Seq analysis during the 2 days prior and 2 days after the boost, and the data were compared with published reports using other strains and growth conditions. During the 2 h after the boost, ϳ425 genes are upregulated >2-fold and ϳ875 genes are downregulated >2-fold in each strain. Expression of a small subset of "sensitive" genes, encoding enzymes involved in the glyoxylate and Calvin-Benson cycles, gluconeogenesis, and the pentose phosphate pathway, is responsive to culture conditions and genetic background as well as to boosting. Four genes-encoding a diacylglycerol acyltransferase (DGTT2), a glycerol-3-P dehydrogenase (GPD3), and two candidate lipases (Cre03.g155250 and Cre17.g735600)-are selectively upregulated in the sta6 strain. Although the bulk rate of acetate depletion from the medium is not boost enhanced, three candidate acetate permease-encoding genes in the GPR1/FUN34/YaaH superfamily are boost upregulated, and 13 of the "sensitive" genes are strongly responsive to the cell's acetate status. A cohort of 64 autophagy-related genes is downregulated by the boost. Our results indicate that the boost serves both to avert an autophagy program and to prolong the operation of key pathways that shuttle carbon from acetate into storage lipid, the combined outcome being enhanced TAG accumulation, notably in the sta6 strain.

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Section: Resultsmentioning

confidence: 99%

The Path to Triacylglyceride Obesity in the sta6 Strain of Chlamydomonas reinhardtii

et al. 2014

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“…The deletion of the family motif NPAPLGL in the Gpr1-2 mutant allele abolishes acetic acid sensitivity and results in the occurrence of only the dephosphorylated form of Gpr1p (Gentsch et al 2007). This is the first hint for a functional significance of this highly conserved family motif.…”

Section: Putative Functionsmentioning

confidence: 98%

“…Also in the three further GPR d mutants B204-12C-38, -124 and -156, the polar amino acids L65Q, G62S and G63D were exchanged, respectively. Surprisingly, deletion and overexpression of GPR1 in Y. lipolytica strains do not induce acetic acid sensitivity and have no obvious phenotypic effects (Augstein 2001) except a prolonged lag phase of growth after transfer into fresh media (Gentsch et al 2007).…”

Section: Putative Functionsmentioning

confidence: 98%

The Gpr1/Fun34/YaaH Protein Family in the Nonconventional Yeast Yarrowia lipolytica and the Conventional Yeast Saccharomyces cerevisiae

Matthäus

Barth

2013

Yarrowia Lipolytica

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The sequencing of the genomes of several organisms was the first step in understanding genome organisation, gene function and of course life itself. Until now very much information could be gained by searching for similarities between genes or structures and finding homologies or direct orthologous genes. But with the sequencing data, more and more questions arise, which cannot be answered by simply looking the data. Although the yeast Saccharomyces cerevisiae was the first eukaryotic organism, the genome of which was sequenced, almost 14 years later there are still 900 uncharacterised and 800 dubious genes (26 % at all). The unconventional yeast Yarrowia lipolytica also harbours a high number of genes with unknown function-ca. 2,300 (35 %). One hundred seventy out of 220 Yarrowia lipolytica specific genes with no homology to other yeasts are also uncharacterised, which should carry the "differences" between the yeast species. So far only 50 industrial useful genes were characterised (proteases, lipases, esterases, etc.).Genes or gene products that do not have any known function have to be analysed in a more classical, genetical way. Especially the functions of membrane proteins which are resistant to a lot of investigation steps are only rarely elucidated. The Gpr1 protein of Yarrowia lipolytica is such an example. The function cannot be estimated by finding similarities to other proteins with known function. The more the information and phenotypic effects are available, the more complex the interacting network appears. This chapter will show the ongoing discovery of the function of the Gpr1/FUN34/YaaH protein family. This is especially shown for the Gpr1 protein from Yarrowia lipolytica and its orthologues in Saccharomyces cerevisiae. Here the different and also controversial facts are reviewed and discussed.

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“…The dominant-negative ATO1 G53D mutation we use here was originally identified in Y. lipolytica, in which it confers sensitivity to acetic acid, as do similar mutations in S. cerevisiae (29,30). Ato proteins are required for active import of acetate in yeast and Aspergillus nidulans (28,67), and the E. coli SatP/YaaH is a succinate/acetate transporter (68).…”

Section: Discussionmentioning

confidence: 99%

“…Though named ATO, for ammonia transport outward (YaaH in bacteria), the molecular function of these plasma membrane proteins is unknown, and there is evidence linking them to transport of acetate in Saccharomyces cerevisiae, Aspergillus nidulans, and Yarrowia lipolytica, as well as release of ammonia in S. cerevisiae (24,(26)(27)(28)(29)(30). Despite the potential for genetic redundancy in this large family, deletion of ATO5 alone retards alkalinization in vitro (24).…”

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confidence: 99%

The Candida albicans ATO Gene Family Promotes Neutralization of the Macrophage Phagolysosome

Danhof

Lorenz

2015

Infect Immun

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Candida albicans is an opportunistic human fungal pathogen that causes a variety of diseases, ranging from superficial mucosal to life-threatening systemic infections, the latter particularly in patients with defects in innate immune function. C. albicans cells phagocytosed by macrophages undergo a dramatic change in their metabolism in which amino acids are a key nutrient. We have shown that amino acid catabolism allows the cell to neutralize the phagolysosome and initiate hyphal growth. We show here that members of the 10-gene ATO family, which are induced by phagocytosis or the presence of amino acids in an Stp2-dependent manner and encode putative acetate or ammonia transporters, are important effectors of this pH change in vitro and in macrophages. When grown with amino acids as the sole carbon source, the deletion of ATO5 or the expression of a dominantnegative ATO1G53D allele results in a delay in alkalinization, a defect in hyphal formation, and a reduction in the amount of ammonia released from the cell. These strains also form fewer hyphae after phagocytosis, have a reduced ability to escape macrophages, and reside in more acidic phagolysosomal compartments than wild-type cells. Furthermore, overexpression of many of the 10 ATO genes accelerates ammonia release, and an ato5⌬ ATO1 G53D double mutant strain has additive alkalinization and ammonia release defects. Taken together, these results indicate that the Ato protein family is a key mediator of the metabolic changes that allow C. albicans to overcome the macrophage innate immunity barrier. Candida albicans is an opportunistic pathogen that colonizes the skin and gastrointestinal and genitourinary tracts of most healthy individuals but also causes a range of diseases, from nonlethal mucosal infections, such as oral thrush and vaginitis, to disseminated hematogenous candidiasis, the latter in immunocompromised individuals (1-3). As the fourth most prevalent cause of hospital-acquired infection, disseminated candidiasis is very difficult to treat, prolongs hospitalization, and has a mortality rate of ϳ40% (4-6). The high mortality rates and large health care burden associated with C. albicans infection highlight the importance of understanding the physiology, virulence factors, and host-pathogen interactions of C. albicans.The healthy immune system is able to effectively prevent systemic candidiasis; however, advances in health care have increased the population of individuals surviving despite immune dysfunctions. Conditions that predispose individuals to disseminated candidiasis include hematological malignancies, genetic immune disorders, HIV/AIDS, and iatrogenic interventions, including organ transplantation, chemotherapy, and invasive procedures (3, 7). The interaction between the innate immune system and C. albicans is a primary determinant of disease progression, as those with innate immune defects are more susceptible to serious infection (8). Macrophages, along with other professional phagocytes, are key components of the innate immune respons...

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Mutations at different sites in members of the Gpr1/Fun34/YaaH protein family cause hypersensitivity to acetic acid inSaccharomyces cerevisiaeas well as inYarrowia lipolytica

Cited by 17 publications

References 33 publications

The Path to Triacylglyceride Obesity in the sta6 Strain of Chlamydomonas reinhardtii

The Path to Triacylglyceride Obesity in the sta6 Strain of Chlamydomonas reinhardtii

The Gpr1/Fun34/YaaH Protein Family in the Nonconventional Yeast Yarrowia lipolytica and the Conventional Yeast Saccharomyces cerevisiae

The Candida albicans ATO Gene Family Promotes Neutralization of the Macrophage Phagolysosome

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