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The significance of peroxisome function in chronological aging of Saccharomyces cerevisiae.

Lefevre SD, van Roermund CW, Wanders RJ, Veenhuis M, van der Klei IJ - Aging Cell (2013)

Bottom Line: We show that intact peroxisomes are an important factor in yeast chronological aging because all pex mutants showed a reduced chronological lifespan.The strongest reduction was observed in Δpex5 cells.Our data indicate that this is related to the complete inactivation of the peroxisomal β-oxidation pathway in these cells due to the mislocalization of thiolase.

View Article: PubMed Central - PubMed

Affiliation: Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, P.O. Box 11103, 9700CC, Groningen, The Netherlands.

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Deletion of PEX7 shortens the lifespan. (A) FACS measurements of H2O2 accumulation using dihydrorhodamine 123 in WT, Δpex3, Δ3'pex5, Δpex3Δpot1, and Δpot1 at day 7 (dark gray) and day 13 (light gray). The graph indicates percentages of positive cells ± SD measured in 20 000 cells per sample from two independent experiments. ***P < 0.005. (B) Effect of PEX7 deletion on chronological lifespan. (C) Mean chronological lifespans of WT and mutant cells. Data represent mean ± SEM from at least two experiments. *P < 0.05; ***P < 0.005.
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fig06: Deletion of PEX7 shortens the lifespan. (A) FACS measurements of H2O2 accumulation using dihydrorhodamine 123 in WT, Δpex3, Δ3'pex5, Δpex3Δpot1, and Δpot1 at day 7 (dark gray) and day 13 (light gray). The graph indicates percentages of positive cells ± SD measured in 20 000 cells per sample from two independent experiments. ***P < 0.005. (B) Effect of PEX7 deletion on chronological lifespan. (C) Mean chronological lifespans of WT and mutant cells. Data represent mean ± SEM from at least two experiments. *P < 0.05; ***P < 0.005.

Mentions: The lifespan of Δpot1 cells (Fig. 4A) is longer compared to that of Δpex3Δpot1 or Δ3'pex5 cells (Table 1). Because in all three strains, the β-oxidation is blocked, additional processes most likely contribute to the reduction of the lifespan of peroxisome-deficient strains. In all three mutant strains, the initial oxidation of fatty acyl-CoA (catalyzed by Pox1) can still occur. This reaction results in the production of hydrogen peroxide, which is decomposed by peroxisomal catalase (Cta1) in WT cells. In Δpex3Δpot1, Δ3'pex5 and Δpex3, where both Pox1 and Cta1 are mislocalized to the cytosol, cells accumulate comparable levels of H2O2 during chronological aging as in Δpot1 cells, in which both enzymes are localized to peroxisomes (Fig. 6A). Hence, the observed differences in CLS of Δpot1 cells and the various pex mutants are unlikely due to differences in cellular H2O2 levels.


The significance of peroxisome function in chronological aging of Saccharomyces cerevisiae.

Lefevre SD, van Roermund CW, Wanders RJ, Veenhuis M, van der Klei IJ - Aging Cell (2013)

Deletion of PEX7 shortens the lifespan. (A) FACS measurements of H2O2 accumulation using dihydrorhodamine 123 in WT, Δpex3, Δ3'pex5, Δpex3Δpot1, and Δpot1 at day 7 (dark gray) and day 13 (light gray). The graph indicates percentages of positive cells ± SD measured in 20 000 cells per sample from two independent experiments. ***P < 0.005. (B) Effect of PEX7 deletion on chronological lifespan. (C) Mean chronological lifespans of WT and mutant cells. Data represent mean ± SEM from at least two experiments. *P < 0.05; ***P < 0.005.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824234&req=5

fig06: Deletion of PEX7 shortens the lifespan. (A) FACS measurements of H2O2 accumulation using dihydrorhodamine 123 in WT, Δpex3, Δ3'pex5, Δpex3Δpot1, and Δpot1 at day 7 (dark gray) and day 13 (light gray). The graph indicates percentages of positive cells ± SD measured in 20 000 cells per sample from two independent experiments. ***P < 0.005. (B) Effect of PEX7 deletion on chronological lifespan. (C) Mean chronological lifespans of WT and mutant cells. Data represent mean ± SEM from at least two experiments. *P < 0.05; ***P < 0.005.
Mentions: The lifespan of Δpot1 cells (Fig. 4A) is longer compared to that of Δpex3Δpot1 or Δ3'pex5 cells (Table 1). Because in all three strains, the β-oxidation is blocked, additional processes most likely contribute to the reduction of the lifespan of peroxisome-deficient strains. In all three mutant strains, the initial oxidation of fatty acyl-CoA (catalyzed by Pox1) can still occur. This reaction results in the production of hydrogen peroxide, which is decomposed by peroxisomal catalase (Cta1) in WT cells. In Δpex3Δpot1, Δ3'pex5 and Δpex3, where both Pox1 and Cta1 are mislocalized to the cytosol, cells accumulate comparable levels of H2O2 during chronological aging as in Δpot1 cells, in which both enzymes are localized to peroxisomes (Fig. 6A). Hence, the observed differences in CLS of Δpot1 cells and the various pex mutants are unlikely due to differences in cellular H2O2 levels.

Bottom Line: We show that intact peroxisomes are an important factor in yeast chronological aging because all pex mutants showed a reduced chronological lifespan.The strongest reduction was observed in Δpex5 cells.Our data indicate that this is related to the complete inactivation of the peroxisomal β-oxidation pathway in these cells due to the mislocalization of thiolase.

View Article: PubMed Central - PubMed

Affiliation: Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, P.O. Box 11103, 9700CC, Groningen, The Netherlands.

Show MeSH
Related in: MedlinePlus