Proteomics identifies organelle specific phosphorylation and reveals major subcellular reorganization in the progression of NAFLD

ABSTRACT: Obesity induced non-alcoholic fatty liver disease (NAFLD) is associated with the development of type 2 diabetes and constitutes a major health problem. A hallmark of the diseases is extensive lipid droplet (LD) formation and accumulation of toxic lipid species interfering with cellular signaling and functions. However, the cellular mechanisms during disease progression and cellular lipid overflow are poorly understood. Here, we develop a novel workflow for label free mass spectrometry based protein and phosphopeptide correlation profiling to systematically monitor the level and cellular distribution of ~6000 liver proteins and ~16,000 phosphosites during the development of dietary induced steatosis in mice. We see a redistribution of the secretory apparatus including a mislocalization of the COPI complex, and targeting of all analyzed Golgi apparatus proteins to LDs what leads to a general reduction of hepatic protein secretion. Further, we identify targeting of several organelle contact site proteins to LDs, accompanied by increased contacts between LDs and other organelles. Our resource provides the first systematic in vivo analysis of subcellular re-arrangements and organelle specific phosphorylation during disease development.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Hepatocyte, Liver

DISEASE(S): Type 2 Diabetes Mellitus,Hepatic Steatosis

SUBMITTER: Natalie Krahmer  

LAB HEAD: Matthias Mann

PROVIDER: PXD007653 | Pride | 2018-10-29

REPOSITORIES: Pride