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PreprintCited by 35Genetics, Aging, and Longevity in Model OrganismsAdvanced Proteomics Techniques and ApplicationsUbiquitin and proteasome pathways

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Global analysis of aging-related protein structural changes uncovers enzyme polymerization-based control of longevity

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Paukštytė, Jurgita, López Cabezas, Rosa María, Feng, Yuehan, Tong, Kai, Schnyder, Daniela, Elomaa, Ellinoora, Gregorova, Pavlina, Doudin, Matteo, Särkkä, Meeri, Sarameri, Jesse, Lippi, Alice, Vihinen, Helena, Juutila, Juhana, Nieminen, Anni, Törönen, Petri, Holm, Liisa, Jokitalo, Eija, Krisko, Anita, Huiskonen, Juha, Sarin, L. Peter, Hietakangas, Ville, Picotti, Paola, Barral, Yves, Saarikangas, Juha·2023·Molecular Cell
DOI 10.1101/2023.01.23.524173

Preprint — published as 10.1016/j.molcel.2023.08.015

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Abstract

Aging is associated with progressive phenotypic changes over time. Virtually all cellular phenotypes are produced by proteins and structural alterations in proteins can lead to age-related diseases. Nonetheless, comprehensive knowledge of proteins undergoing structural-functional changes during cellular aging and their contribution to age-related phenotypes is lacking. Here, we conducted proteome-wide analysis of early age-related protein structural changes in budding yeast using limited proteolysis-mass spectrometry. The results, compiled in online ProtAge-catalog, unravelled age-related functional changes in regulators of translation, protein folding and amino acid metabolism. Mechanistically, we found that folded glutamate synthase Glt1 polymerizes into supramolecular self-assemblies during aging causing breakdown of cellular amino acid homeostasis. Inhibiting Glt1 polymerization by mutating the polymerization interface restored amino acid levels in aged cells, attenuated mitochondrial dysfunction and led to life span extension. Altogether, this comprehensive map of protein structural changes enables identifying novel mechanisms of age-related phenotypes and offers opportunities for their reversal.

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Research works printed but not linked: 99

  1. 10.1146/annurev.genet.40.110405.090412 · DOI · Paper page
  2. 10.1371/journal.pcbi.1006858 · DOI
  3. 10.1016/j.cell.2020.12.021 · DOI
  4. 10.1016/j.trecan.2020.12.006 · DOI
  5. 10.1126/science.aan0346 · DOI · Paper page
  6. 10.1073/pnas.1800168115 · DOI
  7. 10.1016/j.sbi.2014.05.007 · DOI
  8. 10.1038/nrm3920 · DOI
  9. 10.1074/jbc.TM118.001191 · DOI
  10. 10.1038/s41580-020-00326-6 · DOI
  11. 10.1016/j.cell.2013.05.039 · DOI · Paper page
  12. 10.1016/j.ceb.2013.12.003 · DOI
  13. 10.1111/1574-6976.12060 · DOI
  14. 10.1016/j.mad.2018.09.001 · DOI
  15. 10.15698/mic2016.07.510 · DOI
  16. 10.1016/j.cell.2019.01.018 · DOI · Paper page
  17. 10.7554/eLife.41046 · DOI
  18. 10.1074/jbc.M114.600528 · DOI
  19. McFaline-Figueroa, J.R. , Vevea, J. , Swayne, T.C. , Zhou, C. , Liu, C. , Leung, G. , Boldogh, I.R. , and Pon, L.A. (2011). Mitochondrial quality control during inheritance is associated with lifespan and mother-daughter age asymmetry in budding yeast. Aging Cell, 885–895. https://doi.org/10.1111/j.1474-9726.2011.00731.x. · DOI
  20. 10.1038/nature11654 · DOI · Paper page
  21. 10.1126/science.aax9552 · DOI
  22. 10.1101/gad.439307 · DOI
  23. 10.7554/eLife.06633 · DOI
  24. 2021, Molecular damage in aging, Nat Aging, 1, 1096, 10.1038/s43587-021-00150-3 · DOI
  25. 10.1016/j.cell.2016.07.050 · DOI · Paper page
  26. 10.1038/s41586-020-2496-1 · DOI · Paper page
  27. 10.1101/2020.09.04.282525 · DOI
  28. 10.7554/eLife.08527 · DOI
  29. 10.1016/j.cmet.2021.08.017 · DOI · Paper page
  30. 10.1038/s41586-021-04295-4 · DOI
  31. 10.1146/annurev-biochem-060614-033955 · DOI · Paper page
  32. 10.1038/s41580-019-0101-y · DOI · Paper page
  33. 10.1038/s43587-022-00196-x · DOI
  34. 10.1371/journal.pbio.1000450 · DOI · Paper page
  35. 10.1101/2022.02.26.482120 · DOI
  36. 10.1038/s41593-018-0235-9 · DOI · Paper page
  37. 10.1016/j.ceb.2008.09.004 · DOI
  38. 10.1038/nbt.2999 · DOI
  39. 10.1038/nprot.2017.100 · DOI
  40. 10.1126/science.aai7825 · DOI
  41. 10.1016/j.cell.2015.08.041 · DOI
  42. 10.1073/pnas.1416079111 · DOI
  43. 10.1038/s41580-019-0118-2 · DOI · Paper page
  44. 10.7554/elife.39324 · DOI · Paper page
  45. 10.1038/s41580-019-0133-3 · DOI · Paper page
  46. 10.1126/science.272.5268.1606 · DOI
  47. 10.1038/s41594-017-0019-z · DOI
  48. 10.1016/j.cell.2015.05.022 · DOI
  49. 10.1016/j.jmb.2008.08.068 · DOI
  50. 10.1083/jcb.201003001 · DOI
  51. 10.1039/c3mb70508k · DOI
  52. 10.7554/eLife.02409 · DOI
  53. 10.1016/j.jgg.2016.03.008 · DOI
  54. 10.1074/jbc.M708529200 · DOI
  55. 10.1038/nature23320 · DOI · Paper page
  56. 10.1007/s12551-019-00602-6 · DOI
  57. 10.1016/j.yexcr.2020.112383 · DOI
  58. 10.1016/j.cell.2019.12.035 · DOI
  59. 10.1007/s002940050108 · DOI
  60. 10.7554/eLife.64860 · DOI
  61. 10.1016/j.mito.2015.07.001 · DOI
  62. 10.1126/science.aaj2103 · DOI
  63. 10.1002/anie.201806092 · DOI
  64. Mouton, S.N. , Thaller, D.J. , Crane, M.M. , Rempel, I.L. , Terpstra, O.T. , Steen, A. , Kaeberlein, M. , Lusk, C.P. , Boersma, A.J. , and Veenhoff, L.M. (2020). A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast. Elife, e54707. https://doi.org/10.7554/elife.54707. · DOI
  65. 10.1101/2022.03.07.483228 · DOI
  66. 10.7554/elife.02224 · DOI
  67. 10.1073/pnas.1906592116 · DOI · Paper page
  68. 2001, Yeast Cbk1 and Mob2 Activate Daughter-Specific Genetic Programs to Induce Asymmetric Cell Fates, 107, 739
  69. 10.1038/nature02046 · DOI · Paper page
  70. 10.1126/science.aal3321 · DOI · Paper page
  71. 10.1073/pnas.0903503106 · DOI
  72. 10.1002/(SICI)1097-0061(19980130)14:2<115::AID-YEA204>3.0.CO;2-2 · DOI
  73. 10.1534/genetics.109.106229 · DOI
  74. 10.1038/nature02026 · DOI · Paper page
  75. 10.1126/science.285.5429.901 · DOI · Paper page
  76. 10.1002/yea.1142 · DOI
  77. 10.1016/j.cell.2017.09.041 · DOI
  78. 10.1002/yea.3098 · DOI
  79. 10.1371/journal.pone.0183974 · DOI
  80. 10.1002/pro.3943 · DOI
  81. 10.1002/pro.3235 · DOI · Paper page
  82. 10.1016/j.molcel.2012.09.023 · DOI
  83. 10.1093/nar/gky427 · DOI
  84. 10.1006/jmbi.1999.2829 · DOI
  85. 10.1261/rna.048199.114 · DOI
  86. 10.1261/rna.065482.117 · DOI
  87. 10.1080/15476286.2020.1853385 · DOI
  88. 10.1073/pnas.1530509100 · DOI · Paper page
  89. 10.1038/nsmb.3441 · DOI
  90. 10.1093/nar/gks1158 · DOI
  91. 10.1016/j.molcel.2010.06.002 · DOI
  92. 10.1038/nature07743 · DOI
  93. 10.1038/nature04785 · DOI · Paper page
  94. 10.1073/pnas.0635171100 · DOI · Paper page
  95. 10.1093/nar/gkx1042 · DOI · Paper page
  96. 10.1016/j.cmet.2015.09.008 · DOI
  97. 10.1016/j.jprot.2014.10.011 · DOI
  98. 10.1016/j.cell.2015.12.038 · DOI
  99. 10.1038/nature00935 · DOI · Paper page

Metadata

Authors
Paukštytė, J., López Cabezas, R. M., Feng, Y., Tong, K., Schnyder, D., Elomaa, E., Gregorova, P., Doudin, M., Särkkä, M., Sarameri, J., Lippi, A., Vihinen, H., Juutila, J., Nieminen, A., Törönen, P., Holm, L., Jokitalo, E., Krisko, A., Huiskonen, J., Sarin, L. P., Hietakangas, V., Picotti, P., Barral, Y., & Saarikangas, J.
Affiliations
  • University of Helsinki (FI)
  • ETH Zurich (CH)
  • Georgia Institute of Technology (US)
  • Universitätsmedizin Göttingen (DE)
ORCID
Venue
Molecular Cell
Publisher
openRxiv
Published
2023-01-23
Volume
83
Issue
18
Pages
3360-3376.e11
ISSN
1097-2765 (ISSN-L)
DOI
10.1101/2023.01.23.524173
OpenAlex
W4386601044
Cited by
35
References
3
Citations by year
2026: 6 · 2025: 14 · 2024: 12 · 2023: 3
FWCI
2.37
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Cell (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • ETH Zürich Research Collection
Funders
  • Helsingin Yliopisto
  • Human Frontier Science Program (RGY0080/2020)
  • Academy of Finland (317038)
  • Sigrid Juséliuksen Säätiö
  • Helsinki Institute of Life Science, Helsingin Yliopisto
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
cellular aging, protein conformational change, protein polymerization, supramolecular self-assembly, amino acid homeostasis, mitochondrial dysfunction, lifespan extension, translational regulation, protein folding, Saccharomyces cerevisiae, age-related phenotypes
MeSH terms
Amino Acids, Longevity, Cellular Senescence, Polymerization

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