Yeast researchers have long observed asymmetry in cytosolic pH between mother and daughter cells. Likewise, researchers have detailed the accumulation of long-lived asymmetrically retained proteins (LARPs) in mother cells, one of which is the plasma membrane proton pump Pma1p. Pma1p transports protons out of the cytosol, thereby increasing pH, and mother cells show marked increases in vacuolar pH as they age. As mother cells have a shorter replicative life span (RLS) than daughter cells, and aging factors have been linked to pH, it is reasonable to ask whether accumulation of Pma1p itself reduces life span in mother cells.
To address this specific question, Yoon et al. in a 2022 issue of International Journal of Molecular Sciences described screening for suppressors of asymmetric inheritance of Pma1p. They identified three vacuolar protein sorting genes (VPS8, VPS9, and VPS21) for which mutation resulted in high percentages of abnormally symmetric distribution of Pma1p-GFP. As all three of these genes are involved in endocytosis, they asked whether these mutations affected all proteins that are asymmetrically distributed between mother and daughter cells, or just those that reside in the plasma membrane. They found the latter, that the defect is restricted to PM proteins.
Using these mutants with abnormal asymmetric distribution of the proton pump, the authors asked if defects in asymmetric distribution of Pma1p caused changes in aging. Did mother cells without accumulated Pma1p have a longer life span? The answer was a clear “No.” There was little difference in RLS between mutant and wild type, showing that asymmetric distribution of Pma1p does not correlate with aging.
These results are in fact a bit surprising, because aging in mother cells had been previously correlated with a mutation in PMA1 (the pma1-105 allele, Henderson et al., 2014), which increased lifespan by about 30%. Thus, it appears that Pma1p plays a role in aging, but not via asymmetric distribution between mother and daughter cells.
This study adds to what is known about a complicated system. As usual, the awesome power of yeast genetics (#APOYG) provides an excellent forum in which to ask complicated questions in a simple system. Hopefully the links between pH, aging and asymmetry will be revealed in future experiments.