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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Mitra, Kasturi Sengupta, Prabuddha Fu, Dong Arias, Irwin M. Lippincott-schwartz, Jennifer Jarnik, Michal |
| Description | Author Affiliation: Fu D ( Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.); |
| 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 ß-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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 18 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Autophagy Hepatocytes Cytology Metabolism Mitochondria Oxidative Phosphorylation Adenosine Triphosphate Adenylate Kinase Animals Cell Polarity Energy Metabolism Fatty Acids Glycolysis Ultrastructure Lipids Chemistry Membrane Potential, Mitochondrial Mitochondrial Dynamics Mitochondrial Proteins Oxidation-Reduction Up-Regulation Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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