Identification of long-lived proteins reveals exceptional stability of essential cellular structures

Brandon H. Toyama, Jeffrey N. Savas, Sung Kyu Park, Michael S. Harris, Nicholas T. Ingolia, John R. Yates*, Martin W. Hetzer

*Corresponding author for this work

Research output: Contribution to journalArticle

226 Scopus citations

Abstract

Intracellular proteins with long lifespans have recently been linked to age-dependent defects, ranging from decreased fertility to the functional decline of neurons. Why long-lived proteins exist in metabolically active cellular environments and how they are maintained over time remains poorly understood. Here, we provide a system-wide identification of proteins with exceptional lifespans in the rat brain. These proteins are inefficiently replenished despite being translated robustly throughout adulthood. Using nucleoporins as a paradigm for long-term protein persistence, we found that nuclear pore complexes (NPCs) are maintained over a cell's life through slow but finite exchange of even its most stable subcomplexes. This maintenance is limited, however, as some nucleoporin levels decrease during aging, providing a rationale for the previously observed age-dependent deterioration of NPC function. Our identification of a long-lived proteome reveals cellular components that are at increased risk for damage accumulation, linking long-term protein persistence to the cellular aging process. PaperClip

Original languageEnglish (US)
Pages (from-to)971-982
Number of pages12
JournalCell
Volume154
Issue number5
DOIs
StatePublished - Aug 29 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Toyama, B. H., Savas, J. N., Park, S. K., Harris, M. S., Ingolia, N. T., Yates, J. R., & Hetzer, M. W. (2013). Identification of long-lived proteins reveals exceptional stability of essential cellular structures. Cell, 154(5), 971-982. https://doi.org/10.1016/j.cell.2013.07.037