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  Organellar Proteomics and Phospho-Proteomics Reveal Subcellular Reorganization in Diet-Induced Hepatic Steatosis

Krahmer, N., Najafi, B., Schueder, F., Quagliarini, F., Steger, M., Seitz, S., et al. (2018). Organellar Proteomics and Phospho-Proteomics Reveal Subcellular Reorganization in Diet-Induced Hepatic Steatosis. Developmental Cell, 47(2), 205-221.e7. doi:10.1016/j.devcel.2018.09.017.

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Krahmer, Natalie1, Autor           
Najafi, Bahar2, Autor
Schueder, Florian3, Autor           
Quagliarini, Fabiana2, Autor
Steger, Martin1, Autor           
Seitz, Susanne2, Autor
Kasper, Robert4, Autor           
Salinas, Favio5, Autor           
Cox, Jürgen5, Autor           
Uhlenhaut, Nina Henriette2, Autor
Walther, Tobias Christian2, Autor
Jungmann, Ralf3, Autor           
Zeigerer, Anja2, Autor
Borner, Georg Heinz Helmut6, Autor           
Mann, Matthias1, Autor           
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2external, ou_persistent22              
3Jungmann, Ralf / Molecular Imaging and Bionanotechnology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149679              
4MPI of Neurobiology, Max Planck Society, ou_1110547              
5Cox, Jürgen / Computational Systems Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_2063284              
6Borner, Georg / Systems Biology of Membrane Trafficking, Max Planck Institute of Biochemistry, Max Planck Society, ou_3060205              

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Schlagwörter: LIPID DROPLETS; PHOSPHOPROTEOME REVEALS; PROTEIN LOCALIZATION; INSULIN-RESISTANCE; IN-VIVO; LIVER; FAT; PHOSPHORYLATION; QUANTIFICATION; BIOGENESISCell Biology; Developmental Biology;
 Zusammenfassung: Lipid metabolism is highly compartmentalized between cellular organelles that dynamically adapt their compositions and interactions in response to metabolic challenges. Here, we investigate how diet-induced hepatic lipid accumulation, observed in non-alcoholic fatty liver disease (NAFLD), affects protein localization, organelle organization, and protein phosphorylation in vivo. We develop a mass spectrometric workflow for protein and phosphopeptide correlation profiling to monitor levels and cellular distributions of similar to 6,000 liver proteins and similar to 16,000 phosphopeptides during development of steatosis. Several organelle contact site proteins are targeted to lipid droplets (LDs) in steatotic liver, tethering organelles orchestrating lipid metabolism. Proteins of the secretory pathway dramatically redistribute, including the mis-localization of the COPI complex and sequestration of the Golgi apparatus at LDs. This correlates with reduced hepatic protein secretion. Our systematic in vivo analysis of subcellular rearrangements and organelle-specific phosphorylation reveals how nutrient overload leads to organellar reorganization and cellular dysfunction.

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Sprache(n): eng - English
 Datum: 2018
 Publikationsstatus: Erschienen
 Seiten: 24
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: ISI: 000447895000009
DOI: 10.1016/j.devcel.2018.09.017
 Art des Abschluß: -

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Titel: Developmental Cell
Genre der Quelle: Zeitschrift
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Affiliations:
Ort, Verlag, Ausgabe: Cambridge, Mass. : Cell Press
Seiten: - Band / Heft: 47 (2) Artikelnummer: - Start- / Endseite: 205 - 221.e7 Identifikator: ISSN: 1534-5807
CoNE: https://pure.mpg.de/cone/journals/resource/111006902714134