Precisely measured protein lifetimes in the mouse brain reveal differences across tissues and subcellular fractions
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Precisely measured protein lifetimes in the mouse brain reveal differences across tissues and subcellular fractions. / Fornasiero, Eugenio F; Mandad, Sunit; Wildhagen, Hanna; Alevra, Mihai; Rammner, Burkhard; Keihani, Sarva; Opazo, Felipe; Urban, Inga; Ischebeck, Till; Sakib, M Sadman; Fard, Maryam K; Kirli, Koray; Centeno, Tonatiuh Pena; Vidal, Ramon O; Rahman, Raza-Ur; Benito, Eva; Fischer, André; Dennerlein, Sven; Rehling, Peter; Feussner, Ivo; Bonn, Stefan; Simons, Mikael; Urlaub, Henning; Rizzoli, Silvio O.
In: NAT COMMUN, Vol. 9, No. 1, 12.10.2018, p. 4230.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Precisely measured protein lifetimes in the mouse brain reveal differences across tissues and subcellular fractions
AU - Fornasiero, Eugenio F
AU - Mandad, Sunit
AU - Wildhagen, Hanna
AU - Alevra, Mihai
AU - Rammner, Burkhard
AU - Keihani, Sarva
AU - Opazo, Felipe
AU - Urban, Inga
AU - Ischebeck, Till
AU - Sakib, M Sadman
AU - Fard, Maryam K
AU - Kirli, Koray
AU - Centeno, Tonatiuh Pena
AU - Vidal, Ramon O
AU - Rahman, Raza-Ur
AU - Benito, Eva
AU - Fischer, André
AU - Dennerlein, Sven
AU - Rehling, Peter
AU - Feussner, Ivo
AU - Bonn, Stefan
AU - Simons, Mikael
AU - Urlaub, Henning
AU - Rizzoli, Silvio O
PY - 2018/10/12
Y1 - 2018/10/12
N2 - The turnover of brain proteins is critical for organism survival, and its perturbations are linked to pathology. Nevertheless, protein lifetimes have been difficult to obtain in vivo. They are readily measured in vitro by feeding cells with isotopically labeled amino acids, followed by mass spectrometry analyses. In vivo proteins are generated from at least two sources: labeled amino acids from the diet, and non-labeled amino acids from the degradation of pre-existing proteins. This renders measurements difficult. Here we solved this problem rigorously with a workflow that combines mouse in vivo isotopic labeling, mass spectrometry, and mathematical modeling. We also established several independent approaches to test and validate the results. This enabled us to measure the accurate lifetimes of ~3500 brain proteins. The high precision of our data provided a large set of biologically significant observations, including pathway-, organelle-, organ-, or cell-specific effects, along with a comprehensive catalog of extremely long-lived proteins (ELLPs).
AB - The turnover of brain proteins is critical for organism survival, and its perturbations are linked to pathology. Nevertheless, protein lifetimes have been difficult to obtain in vivo. They are readily measured in vitro by feeding cells with isotopically labeled amino acids, followed by mass spectrometry analyses. In vivo proteins are generated from at least two sources: labeled amino acids from the diet, and non-labeled amino acids from the degradation of pre-existing proteins. This renders measurements difficult. Here we solved this problem rigorously with a workflow that combines mouse in vivo isotopic labeling, mass spectrometry, and mathematical modeling. We also established several independent approaches to test and validate the results. This enabled us to measure the accurate lifetimes of ~3500 brain proteins. The high precision of our data provided a large set of biologically significant observations, including pathway-, organelle-, organ-, or cell-specific effects, along with a comprehensive catalog of extremely long-lived proteins (ELLPs).
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/s41467-018-06519-0
DO - 10.1038/s41467-018-06519-0
M3 - SCORING: Journal article
C2 - 30315172
VL - 9
SP - 4230
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -