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The mitochondrial ribosomal protein of the large subunit, Afo1p, determines cellular longevity through mitochondrial back-signaling via TOR1.

Heeren G, Rinnerthaler M, Laun P, von Seyerl P, Kössler S, Klinger H, Hager M, Bogengruber E, Jarolim S, Simon-Nobbe B, Schüller C, Carmona-Gutierrez D, Breitenbach-Koller L, Mück C, Jansen-Dürr P, Criollo A, Kroemer G, Madeo F, Breitenbach M - Aging (Albany NY) (2009)

Bottom Line: Despite the respiratory deficiency the mutant has paradoxical increase in growth rate compared to generic petite mutants.A comparison of the single and double mutant strains for afo1 and fob1 shows that the longevity phenotype of afo1 is independent of the formation of ERCs (ribosomal DNA minicircles).AFO1/MRPL25 function establishes a new connection between mitochondria, metabolism and aging.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Division of Genetics, University of Salzburg, 5020 Salzburg, Austria.

ABSTRACT
Yeast mother cell-specific aging constitutes a model of replicative aging as it occurs in stem cell populations of higher eukaryotes. Here, we present a new long-lived yeast deletion mutation,afo1 (for aging factor one), that confers a 60% increase in replicative lifespan. AFO1/MRPL25 codes for a protein that is contained in the large subunit of the mitochondrial ribosome. Double mutant experiments indicate that the longevity-increasing action of the afo1 mutation is independent of mitochondrial translation, yet involves the cytoplasmic Tor1p as well as the growth-controlling transcription factor Sfp1p. In their final cell cycle, the long-lived mutant cells do show the phenotypes of yeast apoptosis indicating that the longevity of the mutant is not caused by an inability to undergo programmed cell death. Furthermore, the afo1 mutation displays high resistance against oxidants. Despite the respiratory deficiency the mutant has paradoxical increase in growth rate compared to generic petite mutants. A comparison of the single and double mutant strains for afo1 and fob1 shows that the longevity phenotype of afo1 is independent of the formation of ERCs (ribosomal DNA minicircles). AFO1/MRPL25 function establishes a new connection between mitochondria, metabolism and aging.

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Apoptotic                                            markers in old mother cells (fraction V) of the mutant afo1Δ strain. (A)                                            phase contrast; (B) same cell as in A stained with Calcofluor White                                            M2R; (C) the same cell stained with DHE indicating a high level of                                            ROS; (D) an old mother cell stained with FITC-annexin V revealing                                            inversion of the plasma membrane; (E) the same cell as in (D)                                            shows absence of staining with propidium iodide revealing intact plasma                                            membrane; (F) TUNEL staining of old afo1Δ cells.
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Figure 7: Apoptotic markers in old mother cells (fraction V) of the mutant afo1Δ strain. (A) phase contrast; (B) same cell as in A stained with Calcofluor White M2R; (C) the same cell stained with DHE indicating a high level of ROS; (D) an old mother cell stained with FITC-annexin V revealing inversion of the plasma membrane; (E) the same cell as in (D) shows absence of staining with propidium iodide revealing intact plasma membrane; (F) TUNEL staining of old afo1Δ cells.

Mentions: Next, we addressed the question as to whether the longevity phenotype of the afo1 mutation might originate from suppressing the yeast apoptosis pathway. As shown previously [2], old mother cells of the wild type display all of the known markers of yeast apoptosis while these markers are absent from young cells. To tackle this problem, we isolated young (fraction II) and old cells (fraction V) from WT and afo1Δ cells by elutriation centrifugation and tested several markers of apoptosis such as externalization of phosphatidyl serine and DNA strand breaks (Figure 7). Our data clearly indicated that afo1Δ cells did not lose the ability to undergo apoptosis. In spite of a 60% longer median lifespan, senescent mother cells finally succumbed to apoptosis. We conclude that the components of the programmed cell death pathway that a yeast cell has at its disposal, do not cause replicative aging, but that vice versa replicative aging finally leads to cell death via apoptosis.


The mitochondrial ribosomal protein of the large subunit, Afo1p, determines cellular longevity through mitochondrial back-signaling via TOR1.

Heeren G, Rinnerthaler M, Laun P, von Seyerl P, Kössler S, Klinger H, Hager M, Bogengruber E, Jarolim S, Simon-Nobbe B, Schüller C, Carmona-Gutierrez D, Breitenbach-Koller L, Mück C, Jansen-Dürr P, Criollo A, Kroemer G, Madeo F, Breitenbach M - Aging (Albany NY) (2009)

Apoptotic                                            markers in old mother cells (fraction V) of the mutant afo1Δ strain. (A)                                            phase contrast; (B) same cell as in A stained with Calcofluor White                                            M2R; (C) the same cell stained with DHE indicating a high level of                                            ROS; (D) an old mother cell stained with FITC-annexin V revealing                                            inversion of the plasma membrane; (E) the same cell as in (D)                                            shows absence of staining with propidium iodide revealing intact plasma                                            membrane; (F) TUNEL staining of old afo1Δ cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806038&req=5

Figure 7: Apoptotic markers in old mother cells (fraction V) of the mutant afo1Δ strain. (A) phase contrast; (B) same cell as in A stained with Calcofluor White M2R; (C) the same cell stained with DHE indicating a high level of ROS; (D) an old mother cell stained with FITC-annexin V revealing inversion of the plasma membrane; (E) the same cell as in (D) shows absence of staining with propidium iodide revealing intact plasma membrane; (F) TUNEL staining of old afo1Δ cells.
Mentions: Next, we addressed the question as to whether the longevity phenotype of the afo1 mutation might originate from suppressing the yeast apoptosis pathway. As shown previously [2], old mother cells of the wild type display all of the known markers of yeast apoptosis while these markers are absent from young cells. To tackle this problem, we isolated young (fraction II) and old cells (fraction V) from WT and afo1Δ cells by elutriation centrifugation and tested several markers of apoptosis such as externalization of phosphatidyl serine and DNA strand breaks (Figure 7). Our data clearly indicated that afo1Δ cells did not lose the ability to undergo apoptosis. In spite of a 60% longer median lifespan, senescent mother cells finally succumbed to apoptosis. We conclude that the components of the programmed cell death pathway that a yeast cell has at its disposal, do not cause replicative aging, but that vice versa replicative aging finally leads to cell death via apoptosis.

Bottom Line: Despite the respiratory deficiency the mutant has paradoxical increase in growth rate compared to generic petite mutants.A comparison of the single and double mutant strains for afo1 and fob1 shows that the longevity phenotype of afo1 is independent of the formation of ERCs (ribosomal DNA minicircles).AFO1/MRPL25 function establishes a new connection between mitochondria, metabolism and aging.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Division of Genetics, University of Salzburg, 5020 Salzburg, Austria.

ABSTRACT
Yeast mother cell-specific aging constitutes a model of replicative aging as it occurs in stem cell populations of higher eukaryotes. Here, we present a new long-lived yeast deletion mutation,afo1 (for aging factor one), that confers a 60% increase in replicative lifespan. AFO1/MRPL25 codes for a protein that is contained in the large subunit of the mitochondrial ribosome. Double mutant experiments indicate that the longevity-increasing action of the afo1 mutation is independent of mitochondrial translation, yet involves the cytoplasmic Tor1p as well as the growth-controlling transcription factor Sfp1p. In their final cell cycle, the long-lived mutant cells do show the phenotypes of yeast apoptosis indicating that the longevity of the mutant is not caused by an inability to undergo programmed cell death. Furthermore, the afo1 mutation displays high resistance against oxidants. Despite the respiratory deficiency the mutant has paradoxical increase in growth rate compared to generic petite mutants. A comparison of the single and double mutant strains for afo1 and fob1 shows that the longevity phenotype of afo1 is independent of the formation of ERCs (ribosomal DNA minicircles). AFO1/MRPL25 function establishes a new connection between mitochondria, metabolism and aging.

Show MeSH
Related in: MedlinePlus