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At neutral pH the chronological lifespan of Hansenula polymorpha increases upon enhancing the carbon source concentrations.

ABSTRACT: Dietary restriction is generally assumed to increase the lifespan in most eukaryotes, including the simple model organism Saccharomyces cerevisiae. However, recent data questioned whether this phenomenon is indeed true for yeast. We studied the effect of reduction of the carbon source concentration on the chronological lifespan of the yeast Hansenula polymorpha using four different carbon sources. Our data indicate that reduction of the carbon source concentration has a negative (glucose, ethanol, methanol) or positive (glycerol) effect on the chronological lifespan. We show that the actual effect of carbon source concentrations largely depends on extracellular factor(s). We provide evidence that H. polymorpha acidifies the medium and that a low pH of the medium alone is sufficient to significantly decrease the chronological lifespan. However, glucose-grown cells are less sensitive to low pH compared to glycerol-grown cells, explaining why only the reduction of the glycerol-concentration (which leads to less medium acidification) has a positive effect on the chronological lifespan. Instead, the positive effect of enhancing the glucose concentrations is much larger than the negative effect of the medium acidification at these conditions, explaining the increased lifespan with increasing glucose concentrations. Importantly, at neutral pH, the chronological lifespan also decreases with a reduction in glycerol concentrations. We show that for glycerol cultures this effect is related to acidification independent changes in the composition of the spent medium. Altogether, our data indicate that in H. polymorpha at neutral pH the chronological lifespan invariably extends upon increasing the carbon source concentration.

SUBMITTER: Kawalek A

PROVIDER: S-EPMC5354561 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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At neutral pH the chronological lifespan of Hansenula polymorpha increases upon enhancing the carbon source concentrations.

Kawałek Adam A van der Klei Ida J IJ

Microbial cell (Graz, Austria) 20140520 6

Dietary restriction is generally assumed to increase the lifespan in most eukaryotes, including the simple model organism Saccharomyces cerevisiae. However, recent data questioned whether this phenomenon is indeed true for yeast. We studied the effect of reduction of the carbon source concentration on the chronological lifespan of the yeast Hansenula polymorpha using four different carbon sources. Our data indicate that reduction of the carbon source concentration has a negative (g ...[more]

PMID: 28357243

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Project description:BACKGROUND: Methylotrophic yeast species (e.g. Hansenula polymorpha, Pichia pastoris) can grow on methanol as sole source of carbon and energy. These organisms are important cell factories for the production of recombinant proteins, but are also used in fundamental research as model organisms to study peroxisome biology. During exponential growth on glucose, cells of H. polymorpha typically contain a single, small peroxisome that is redundant for growth while on methanol multiple, enlarged peroxisomes are present. These organelles are crucial to support growth on methanol, as they contain key enzymes of methanol metabolism.In this study, changes in the transcriptional profiles during adaptation of H. polymorpha cells from glucose- to methanol-containing media were investigated using DNA-microarray analyses. RESULTS: Two hours after the shift of cells from glucose to methanol nearly 20% (1184 genes) of the approximately 6000 annotated H. polymorpha genes were significantly upregulated with at least a two-fold differential expression. Highest upregulation (> 300-fold) was observed for the genes encoding the transcription factor Mpp1 and formate dehydrogenase, an enzyme of the methanol dissimilation pathway. Upregulated genes also included genes encoding other enzymes of methanol metabolism as well as of peroxisomal beta-oxidation.A moderate increase in transcriptional levels (up to 4-fold) was observed for several PEX genes, which are involved in peroxisome biogenesis. Only PEX11 and PEX32 were higher upregulated. In addition, an increase was observed in expression of the several ATG genes, which encode proteins involved in autophagy and autophagy processes. The strongest upregulation was observed for ATG8 and ATG11.Approximately 20% (1246 genes) of the genes were downregulated. These included glycolytic genes as well as genes involved in transcription and translation. CONCLUSION: Transcriptional profiling of H. polymorpha cells shifted from glucose to methanol showed the expected downregulation of glycolytic genes together with upregulation of the methanol utilisation pathway. This serves as a confirmation and validation of the array data obtained. Consistent with this, also various PEX genes were upregulated. The strong upregulation of ATG genes is possibly due to induction of autophagy processes related to remodeling of the cell architecture required to support growth on methanol. These processes may also be responsible for the enhanced peroxisomal beta-oxidation, as autophagy leads to recycling of membrane lipids. The prominent downregulation of transcription and translation may be explained by the reduced growth rate on methanol (td glucose 1 h vs td methanol 4.5 h).

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At neutral pH the chronological lifespan of Hansenula polymorpha increases upon enhancing the carbon source concentrations.

Publications

At neutral pH the chronological lifespan of <i>Hansenula polymorpha</i> increases upon enhancing the carbon source concentrations.

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