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1.
FEBS Lett ; 597(18): 2316-2333, 2023 09.
Article in English | MEDLINE | ID: mdl-37574219

ABSTRACT

We previously found that overexpression of phosphate starvation-responsive genes by disrupting PHO80 led to a shortened replicative lifespan in yeast. To identify lifespan-related genes, we screened upregulated genes in the pho80Δ mutant and focused on the VTC genes, which encode the vacuolar polyphosphate (polyP) polymerase complex. VTC1/VTC2/VTC4 deletion restored the lifespan and intracellular polyP levels in pho80Δ. In the wild type, overexpression of VTC5 or a combination of the other VTCs caused high polyP accumulation and shortened lifespan. Similar phenotypes were caused by the deletion of polyP phosphatase genes-vacuolar PPN1 and cytosolic PPX1. The polyP-accumulating strains exhibited stress sensitivities. Thus, we demonstrated that polyP metabolic enzymes participate in replicative lifespan, and extreme polyP accumulation shortens the lifespan.


Subject(s)
Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolism , Polyphosphates/metabolism , Phosphoric Monoester Hydrolases/genetics , Phosphoric Monoester Hydrolases/metabolism , Longevity/genetics , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism
2.
FEBS Lett ; 594(7): 1166-1175, 2020 04.
Article in English | MEDLINE | ID: mdl-31797348

ABSTRACT

Lifespan is determined by genetic factors and influenced by environmental factors. Here, we find that the phosphate signal transduction (PHO) pathway is involved in the determination of replicative lifespan in budding yeast. Extracellular phosphate does not affect the lifespan. However, deletion of PHO80 (cyclin) and PHO85 (cyclin-dependent kinase) genes, that is, negative regulators of the PHO pathway, shortens the lifespan, which is restored by further deletion of PHO4 (transcriptional activator). Four of the other nine Pho85p cyclin genes are also required to maintain normal lifespan. The short-lived mutants show a metabolic profile that is similar to strains with normal lifespan. Thus, Pho85p kinase genetically determines replicative lifespan in combination with relevant cyclins. Our findings uncover novel cellular signals in longevity regulation.


Subject(s)
Cellular Senescence , Cyclin-Dependent Kinases/metabolism , Cyclins/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/metabolism , Cell Division/drug effects , Cellular Senescence/genetics , Cyclins/genetics , HSP70 Heat-Shock Proteins/genetics , Mutant Proteins/genetics , Mutant Proteins/metabolism , Mutation , Phosphates/metabolism , Phosphates/pharmacology , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/enzymology , Saccharomyces cerevisiae Proteins/genetics
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