Altering nuclear pore complex function impacts longevity and mitochondrial function in S. cerevisiae.
Bottom Line: Mutants lacking the GLFG domain of Nup116 displayed decreased RLSs, whereas longevity was increased in nup100- mutants.Both Kap121-dependent transport and Nup116 levels decrease in replicatively aged yeast.Together, these studies reveal that specific NPC nuclear transport events directly influence aging.
Affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.Show MeSH
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Mentions: Our results are consistent with a model whereby NPC damage contributes to the aging process in wild-type cells (Fig. 7). Replicatively aged NPCs likely contain partially degraded Nups because full-length Nup116 and Nsp1 levels are decreased in aged cells (Fig. 3 B), even though Nsp1-GFP still localizes to the nuclear rim (Fig. 3 D). Loss of Nup116’s GLFG domain then inhibits Kap121-dependent nuclear import (Fig. 2 B), which compromises mitochondrial function (Figs. 5 and 6) and decreases RLS (Figs. 1 A and 2 D). We speculate that deletion of Nup116’s GLFG domain promotes aging because Kap121-mediated transport is inhibited in young cells, limiting the function of their mitochondria and replicative potential during the aging process. RLS is further reduced in nup116ΔGLFG nup145ΔGLFG cells because of functional redundancy between the GLFG domains of Nup145 and Nup116 (Fig. 1 A). Overexpression of GSP1 suppresses mitochondrial defects in nup116ΔGLFG cells and thus extends the RLS in mutant cells. We hypothesize that GSP1 overexpression increases RLS in wild-type cells by limiting some of the nuclear transport defects observed in aged cells.
Affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.