title: Coordinated elevation of mitochondrial oxidative phosphorylation and autophagy help drive hepatocyte polarization.
abstract: Cell polarization requires increased cellular energy and metabolic output, but how these energetic demands are met by polarizing cells is unclear. To address these issues, we investigated the roles of mitochondrial bioenergetics and autophagy during cell polarization of hepatocytes cultured in a collagen sandwich system. We found that as the hepatocytes begin to polarize, they use oxidative phosphorylation to raise their ATP levels, and this energy production is required for polarization. After the cells are polarized, the hepatocytes shift to become more dependent on glycolysis to produce ATP. Along with this central reliance on oxidative phosphorylation as the main source of ATP production in polarizing cultures, several other metabolic processes are reprogrammed during the time course of polarization. As the cells polarize, mitochondria elongate and mitochondrial membrane potential increases. In addition, lipid droplet abundance decreases over time. These findings suggest that polarizing cells are reliant on fatty acid oxidation, which is supported by pharmacologic inhibition of β-oxidation by etomoxir. Finally, autophagy is up-regulated during cell polarization, with inhibition of autophagy retarding cell polarization. Taken together, our results describe a metabolic shift involving a number of coordinated metabolic pathways that ultimately serve to increase energy production during cell polarization.
authors.affiliation: Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Fu
authors.forename: Kasturi
authors.initials: K
authors.lastname: Mitra
authors.forename: Prabuddha
authors.initials: P
authors.lastname: Sengupta
authors.forename: Michal
authors.initials: M
authors.lastname: Jarnik
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lippincott-Schwartz
authors.forename: Irwin M
authors.initials: IM
authors.lastname: Arias
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D016764:Cell Polarity; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D006019:Glycolysis; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D008055:Lipids / Q000737:chemistry; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D051381:Rats; D015854:Up-Regulation
chemical_list: D005227:Fatty Acids; D008055:Lipids; D024101:Mitochondrial Proteins; D000255:Adenosine Triphosphate; D000263:Adenylate Kinase