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

The Journal of Cell Biology
Christopher L LordSusan R Wente

Abstract

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.

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Citations

Oct 7, 2015·Trends in Cell Biology·Brant M Webster, C Patrick Lusk
Oct 5, 2016·The Journal of Cell Biology·Benjamin L TimneyMichael P Rout
Jan 9, 2020·The FEBS Journal·Irina L RempelLiesbeth M Veenhoff
Sep 20, 2019·Current Genetics·Riddhi BanerjeeShirisha Nagotu
Jan 10, 2020·Current Genetics·Grant A King, Elçin Ünal
May 27, 2020·The Journal of Cell Biology·Yui TomiokaHitoshi Nakatogawa
Jul 22, 2018·Biochemical Society Transactions·David J Thaller, C Patrick Lusk
May 18, 2020·Journal of Huntington's Disease·Emily Machiela, Amber L Southwell
Jun 13, 2020·Biomolecules·Rashmi DahiyaMd Imtaiyaz Hassan
Jul 8, 2016·Molecular Biology of the Cell·Gregory C Howard, William P Tansey
Jun 17, 2020·Ageing Research Reviews·Alexander Fedintsev, Alexey Moskalev
Oct 15, 2020·The Journal of Cell Biology·Christopher L Lord, Susan R Wente
Apr 29, 2021·The Journal of Cell Biology·Tae Yeon Yoo, Timothy J Mitchison
Sep 4, 2020·Experimental Cell Research·Jay S GoodmanElçin Ünal

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Methods Mentioned

BETA
fluorescence microscopy
PCR
confocal microscopy

Software Mentioned

NIS Elements AR
Prism
AxioVision
NIS Elements Advanced Research
Photoshop
GraphPad
ImageJ

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