Asymmetrically inherited multidrug resistance transporters are recessive determinants in cellular replicative ageing View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-08

AUTHORS

Amr Eldakak, Giulia Rancati, Boris Rubinstein, Parama Paul, Veronica Conaway, Rong Li

ABSTRACT

Cellular ageing is known to correlate with the accumulation of many harmful agents, 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. More... »

PAGES

799

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncb2085

DOI

http://dx.doi.org/10.1038/ncb2085

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1046648196

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20657593


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