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: Because Kap121 transport was mediated by Nup116’s GLFG domain (Fig. 2), kap121-7 and kap121-21 mutants were analyzed to determine whether they also displayed inhibited mitochondrial activity. This possibility seemed likely as KAP121 was isolated in an overexpression screen for genes that enhance the import of hydrophobic membrane proteins into the mitochondria (Corral-Debrinski et al., 1999). Both kap121-7 and kap121-21 cells were not viable on glycerol at 25°C (Fig. 6 A), indicative of strong defects in mitochondrial function. Quantification of MitoTracker red CMXRos staining showed the ΔΨ of kap121-7 and kap121-21 mutants was significantly decreased compared with wild-type cells (Fig. 6, B and C). When the brightness was adjusted to help visualize MitoTracker signal in kap121 mutants, the mitochondria also often appeared more fragmented compared with wild-type cells (Fig. S5 E).
Affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.