The mitochondrial ribosomal protein of the large subunit, Afo1p, determines cellular longevity through mitochondrial back-signaling via TOR1.
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.
Heeren
Gino
G
Department of Cell Biology, Division of Genetics, University of Salzburg, 5020 Salzburg, Austria.
Rinnerthaler
Mark
M
Laun
Peter
P
von Seyerl
Phyllis
P
Kössler
Sonja
S
Klinger
Harald
H
Hager
Matthias
M
Bogengruber
Edith
E
Jarolim
Stefanie
S
Simon-Nobbe
Birgit
B
Schüller
Christoph
C
Carmona-Gutierrez
Didac
D
Breitenbach-Koller
Lore
L
Mück
Christoph
C
Jansen-Dürr
Pidder
P
Criollo
Alfredo
A
Kroemer
Guido
G
Madeo
Frank
F
Breitenbach
Michael
M
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D048429:Cell Size; D003433:Crosses, Genetic; D004270:DNA, Circular / Q000235:genetics / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D004270:DNA, Circular; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D006861:Hydrogen Peroxide; D024101:Mitochondrial Proteins; D016877:Oxidants; D019869:Phosphatidylinositol 3-Kinases; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; D020122:tert-Butylhydroperoxide; C105579:FOB1 protein, S cerevisiae; C077889:MRP17 protein, S cerevisiae; C068358:MRPL25 protein, S cerevisiae; C117421:SFP1 protein, S cerevisiae; C083324:TOR1 protein, S cerevisiae