Author: ["Amr Eldakak","Giulia Rancati","Boris Rubinstein","Parama Paul","Veronica Conaway","Rong Li"]
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Abstract
During yeast cell division, multidrug resistance (MDR) transporters partition unequally, with the older pool remaining in the mother cell. Mutations in MDR transporter genes reduce replicative lifespan, whereas an extra copy of these genes extends it, suggesting that defective MDR proteins may influence replicative ageing. Cellular ageing is known to correlate with the accumulation of many harmful agents1, but it is unclear whether ageing can also result from the deterioration of components that are beneficial to the cell, but have a low rate of renewal. Here, we report a group of plasma membrane-associated transporters in yeast, belonging to the multidrug resistance (MDR) protein families, that may represent the latter type of ageing determinants. During the division of a yeast cell, newly synthesized transporter proteins are deposited mostly into the growing bud, whereas previously synthesized MDR proteins remain tightly associated with the mother cortex. Thus, the new and old pools of membrane-bound MDR proteins are spatially segregated during yeast asymmetric cell division, with the older pool stably inherited by the ageing mother. A model based on the observed dynamics of MDR protein inheritance and turnover predicted a decline in MDR activity as the mother cell advances in replicative age. As MDR proteins have crucial roles in cellular metabolism, detoxification and stress response, their collective decline may lead to fitness loss at an advanced age. Supporting this hypothesis, mutants lacking certain MDR genes exhibited a reduced replicative lifespan (RLS), whereas introduction of only one extra copy of these MDR genes extended RLS.Cite this article
Eldakak, A., Rancati, G., Rubinstein, B. et al. Asymmetrically inherited multidrug resistance transporters are recessive determinants in cellular replicative ageing. Nat Cell Biol 12, 799–805 (2010). https://doi.org/10.1038/ncb2085 