title: Mother-daughter asymmetry of pH underlies aging and rejuvenation in yeast.
abstract: Replicative aging in yeast is asymmetric-mother cells age but their daughter cells are rejuvenated. Here we identify an asymmetry in pH between mother and daughter cells that underlies aging and rejuvenation. Cytosolic pH increases in aging mother cells, but is more acidic in daughter cells. This is due to the asymmetric distribution of the major regulator of cytosolic pH, the plasma membrane proton ATPase (Pma1). Pma1 accumulates in aging mother cells, but is largely absent from nascent daughter cells. We previously found that acidity of the vacuole declines in aging mother cells and limits lifespan, but that daughter cell vacuoles re-acidify. We find that Pma1 activity antagonizes mother cell vacuole acidity by reducing cytosolic protons. However, the inherent asymmetry of Pma1 increases cytosolic proton availability in daughter cells and facilitates vacuole re-acidification and rejuvenation.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
authors.forename: Kiersten A
authors.identifier: http://orcid.org/0000-0002-2295-1232
authors.initials: KA
authors.lastname: Henderson
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
authors.forename: Adam L
authors.identifier: http://orcid.org/0000-0002-7095-3793
authors.initials: AL
authors.lastname: Hughes
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
authors.forename: Daniel E
authors.identifier: http://orcid.org/0000-0002-7303-6552
authors.initials: DE
authors.lastname: Gottschling
mesh_terms: D000143:Acids / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D048749:Cytokinesis; D003600:Cytosol / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006180:Proton-Translocating ATPases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013997:Time Factors; D014617:Vacuoles / Q000378:metabolism
chemical_list: D000143:Acids; D029701:Saccharomyces cerevisiae Proteins; C092477:PMA1 protein, S cerevisiae; D006180:Proton-Translocating ATPases
keywords: H+-ATPase; S. cerevisiae; aging; asymmetry; cell biology; developmental biology; pH; rejuvenation; stem cells; vacuole