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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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Old and young cells of the same strains as                                        in A were isolated by elutriation centrifugation and                                        ERCs were analyzed by gel electrophoresis and Southern blotting                                        with an rDNA-specific probe as described in [19]. Thick arrow:                                        chromosomal rDNA repeats; Thin arrow: ERCs (minicircles).                                        Taken together, the results presented in this figure indicate                                        that longevity in the afo1Δ strain is not influenced by the                                        fob1-deletion or the presence of ERCs.
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F8B: Old and young cells of the same strains as in A were isolated by elutriation centrifugation and ERCs were analyzed by gel electrophoresis and Southern blotting with an rDNA-specific probe as described in [19]. Thick arrow: chromosomal rDNA repeats; Thin arrow: ERCs (minicircles). Taken together, the results presented in this figure indicate that longevity in the afo1Δ strain is not influenced by the fob1-deletion or the presence of ERCs.

Mentions: However, we observed a similar median life span of the fob1Δ, afo1Δ double mutant and the afo1Δ mutant cells (Figure 8A). As an internal control, both the fob1Δ single mutant and the fob1Δ, afo1Δ double mutant exhibited the absence of ERCs even in fraction IV and V old cells, while a continuous age-dependent increase in ERCs was found, in particular in fraction IV and V senescent mother cells from WT and afo1Δ cells (Figure 8B). Thus, the lifespan-extension observed in the afo1Δ strain occurs in the presence of ERCs and is not further increased when ERCs are absent, consequently ERCs do not influence longevity in the afo1Δ strain.


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)

Old and young cells of the same strains as                                        in A were isolated by elutriation centrifugation and                                        ERCs were analyzed by gel electrophoresis and Southern blotting                                        with an rDNA-specific probe as described in [19]. Thick arrow:                                        chromosomal rDNA repeats; Thin arrow: ERCs (minicircles).                                        Taken together, the results presented in this figure indicate                                        that longevity in the afo1Δ strain is not influenced by the                                        fob1-deletion or the presence of ERCs.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

F8B: Old and young cells of the same strains as in A were isolated by elutriation centrifugation and ERCs were analyzed by gel electrophoresis and Southern blotting with an rDNA-specific probe as described in [19]. Thick arrow: chromosomal rDNA repeats; Thin arrow: ERCs (minicircles). Taken together, the results presented in this figure indicate that longevity in the afo1Δ strain is not influenced by the fob1-deletion or the presence of ERCs.
Mentions: However, we observed a similar median life span of the fob1Δ, afo1Δ double mutant and the afo1Δ mutant cells (Figure 8A). As an internal control, both the fob1Δ single mutant and the fob1Δ, afo1Δ double mutant exhibited the absence of ERCs even in fraction IV and V old cells, while a continuous age-dependent increase in ERCs was found, in particular in fraction IV and V senescent mother cells from WT and afo1Δ cells (Figure 8B). Thus, the lifespan-extension observed in the afo1Δ strain occurs in the presence of ERCs and is not further increased when ERCs are absent, consequently ERCs do not influence longevity in the afo1Δ strain.

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