The mitochondrial ribosomal of the large subunit, afo1p, determines cellular longevity through mitochondrial back-signaling via TOR1

Abstract: Yeast mother cell‐specific aging constitutes a model of replicative aging as it occurs in stem cell populations ofhigher eukaryotes. Here, we present a new long‐lived yeast deletion mutation, afo1 (for aging factor one), that confers a60% increase in replicative lifespan. AFO1/MRPL25 codes for a protein that is contained in the large subunit of themitochondrial ribosome. Double mutant experiments indicate that the longevity‐increasing action of the afo1 mutation isindependent of mitochondrial translation, yet involves the cytoplasmic Tor1p as well as the growth‐controllingtranscription factor Sfp1p. In their final cell cycle, the long‐lived mutant cells do show the phenotypes of yeast apoptosisindicating that the longevity of the mutant is not caused by an inaility to undergo programmed cell death. Furthermore,the afo1 mutation displays high resistance against oxidants. Despite the respiratory deficiency the mutant has paradoxicalincrease in growth rate compared to generic petite mutants. A comparison of the single and double mutant strains for afo1and fob1 shows that the longevity phenotype of afo1 is independen of the formation of ERCs (ribosomal DNA minicircles).AFO1/MRPL25 function establishes a new connection between mitochondria, metabolism and aging.