Identification of long-lived proteins reveals exceptional stability of essential cellular structures Toyama, Brandon H. Savas, Jeffrey N. Park, Sung Kyu Harris, Michael S. Ingolia, Nicholas T. Yates, John R. HETZER, Martin W ; https://orcid.org/0000-0002-2111-992X General Biochemistry Genetics and Molecular Biology 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. Elsevier 2013 info:eu-repo/semantics/article doc-type:article text http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/11087 Toyama BH, Savas JN, Park SK, et al. Identification of long-lived proteins reveals exceptional stability of essential cellular structures. <i>Cell</i>. 2013;154(5):971-982. doi:<a href="https://doi.org/10.1016/j.cell.2013.07.037">10.1016/j.cell.2013.07.037</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2013.07.037 info:eu-repo/semantics/altIdentifier/issn/0092-8674 info:eu-repo/semantics/altIdentifier/pmid/23993091 info:eu-repo/semantics/openAccess