title: Mechanisms of In Vivo Ribosome Maintenance Change in Response to Nutrient Signals.
abstract: Control of protein homeostasis is fundamental to the health and longevity of all organisms. Because the rate of protein synthesis by ribosomes is a central control point in this process, regulation, and maintenance of ribosome function could have amplified importance in the overall regulatory circuit. Indeed, ribosomal defects are commonly associated with loss of protein homeostasis, aging, and disease (1-4), whereas improved protein homeostasis, implying optimal ribosomal function, is associated with disease resistance and increased lifespan (5-7). To maintain a high-quality ribosome population within the cell, dysfunctional ribosomes are targeted for autophagic degradation. It is not known if complete degradation is the only mechanism for eukaryotic ribosome maintenance or if they might also be repaired by replacement of defective components. We used stable-isotope feeding and protein mass spectrometry to measure the kinetics of turnover of ribosomal RNA (rRNA) and 71 ribosomal proteins (r-proteins) in mice. The results indicate that exchange of individual proteins and whole ribosome degradation both contribute to ribosome maintenance in vivo In general, peripheral r-proteins and those with more direct roles in peptide-bond formation are replaced multiple times during the lifespan of the assembled structure, presumably by exchange with a free cytoplasmic pool, whereas the majority of r-proteins are stably incorporated for the lifetime of the ribosome. Dietary signals impact the rates of both new ribosome assembly and component exchange. Signal-specific modulation of ribosomal repair and degradation could provide a mechanistic link in the frequently observed associations among diminished rates of protein synthesis, increased autophagy, and greater longevity (5, 6, 8, 9).
authors.affiliation: From the ‡Department of Chemistry and Biochemistry.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mathis
authors.affiliation: From the ‡Department of Chemistry and Biochemistry.
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Naylor
authors.affiliation: From the ‡Department of Chemistry and Biochemistry.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Carson
authors.affiliation: From the ‡Department of Chemistry and Biochemistry.
authors.forename: Eric
authors.initials: E
authors.lastname: Evans
authors.affiliation: From the ‡Department of Chemistry and Biochemistry.
authors.forename: Justin
authors.initials: J
authors.lastname: Harwell
authors.affiliation: From the ‡Department of Chemistry and Biochemistry.
authors.forename: Jared
authors.initials: J
authors.lastname: Knecht
authors.affiliation: From the ‡Department of Chemistry and Biochemistry.
authors.forename: Eric
authors.initials: E
authors.lastname: Hexem
authors.affiliation: §Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado 80523.
authors.forename: Fredrick F
authors.initials: FF
authors.lastname: Peelor
authors.affiliation: §Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado 80523.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Miller
authors.affiliation: §Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado 80523.
authors.forename: Karyn L
authors.initials: KL
authors.lastname: Hamilton
authors.affiliation: ¶Department of Physics and Astronomy.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Transtrum
authors.affiliation: ‖Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah 84602.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Bikman
authors.affiliation: From the ‡Department of Chemistry and Biochemistry, jcprice@chem.byu.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Price
mesh_terms: D000818:Animals; D001343:Autophagy; D004032:Diet; D007553:Isotope Labeling; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D012335:RNA, Ribosomal / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D012335:RNA, Ribosomal; D012269:Ribosomal Proteins