Organellar proteomics and phospho-proteomics reveal subcellular reorganization 
in diet-induced hepatic steatosis

Krahmer, Natalie; Najafi, Bahar; Schueder, Florian; Quagliarini, Fabiana; Steger, Martin; Seitz, Susanne; Kasper, Robert; Salinas, Favio; Cox, Jürgen; Uhlenhaut, Nina Henriette; Walther, Tobias Christian; Jungmann, Ralf; Zeigerer, Anja; Borner, Georg Heinz Helmut; Mann, Matthias

doi:10.1016/j.devcel.2018.09.017

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Organellar proteomics and phospho-proteomics reveal subcellular reorganization in diet-induced hepatic steatosis

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Krahmer, Natalie
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons197583

Schueder, Florian
Jungmann, Ralf / Molecular Imaging and Bionanotechnology, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons195396

Steger, Martin
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons211298

Kasper, Robert
MPI of Neurobiology, Max Planck Society;

/persons/resource/persons227241

Salinas, Favio
Cox, Jürgen / Computational Systems Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons77870

Cox, Jürgen
Cox, Jürgen / Computational Systems Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons172959

Jungmann, Ralf
Jungmann, Ralf / Molecular Imaging and Bionanotechnology, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons136451

Borner, Georg Heinz Helmut
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons78356

Mann, Matthias
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

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.

Cite as: https://hdl.handle.net/21.11116/0000-0003-72E7-8

Abstract

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.