Altering nuclear pore complex function impacts longevity and mitochondrial function in S. cerevisiae.

Lord CL, Timney BL, Rout MP, Wente SR
J Cell Biol. 2015 208 (6): 729-44

PMID: 25778920 · PMCID: PMC4362458 · DOI:10.1083/jcb.201412024

The eukaryotic nuclear permeability barrier and selective nucleocytoplasmic transport are maintained by nuclear pore complexes (NPCs), large structures composed of ∼ 30 proteins (nucleoporins [Nups]). NPC structure and function are disrupted in aged nondividing metazoan cells, although it is unclear whether these changes are a cause or consequence of aging. Using the replicative life span (RLS) of Saccharomyces cerevisiae as a model, we find that specific Nups and transport events regulate longevity independent of changes in NPC permeability. Mutants lacking the GLFG domain of Nup116 displayed decreased RLSs, whereas longevity was increased in nup100-null mutants. We show that Nup116 mediates nuclear import of the karyopherin Kap121, and each protein is required for mitochondrial function. Both Kap121-dependent transport and Nup116 levels decrease in replicatively aged yeast. Overexpression of GSP1, the small GTPase that powers karyopherin-mediated transport, rescued mitochondrial and RLS defects in nup116 mutants and increased longevity in wild-type cells. Together, these studies reveal that specific NPC nuclear transport events directly influence aging.

© 2015 Lord et al.

MeSH Terms (13)

Active Transport, Cell Nucleus Cell Nucleus Membrane Transport Proteins Microbial Viability Mitochondria Monomeric GTP-Binding Proteins Nuclear Pore Nuclear Pore Complex Proteins Nuclear Proteins Permeability Receptors, Cytoplasmic and Nuclear Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins

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