Anabolism-Associated Mitochondrial Stasis Driving Lymphocyte Differentiation over Self-Renewal
| Autor: | Ulf Klein, Bonnie Yen, Larry L. Luchsinger, Steven L. Reiner, Yen-Hua Chen, Jeffrey C. Rathmell, Hans-Willem Snoeck, Nyanza J. Rothman, Meinrad Busslinger, Simone A. Nish, William C. Adams, Wen-Hsuan W. Lin, Radomir Kratchmarov |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Anabolism Cell fate determination Biology Mitochondrion Lymphocyte Activation self-renewal General Biochemistry Genetics and Molecular Biology Article asymmetric cell division 03 medical and health sciences Mice Phosphatidylinositol 3-Kinases Autophagy Animals Regeneration Lymphocytes TCF1 lcsh:QH301-705.5 PI3K/AKT/mTOR pathway Pax5 Catabolism Forkhead Box Protein O1 TOR Serine-Threonine Kinases Lymphocyte differentiation Cell Differentiation Hematopoiesis Mitochondria stem cell Metabolic pathway 030104 developmental biology Metabolism Biochemistry lcsh:Biology (General) Anaerobic glycolysis Interferon Regulatory Factors Warburg effect Reactive Oxygen Species Glycolysis Signal Transduction |
| Zdroj: | Cell Reports, Vol 17, Iss 12, Pp 3142-3152 (2016) |
| ISSN: | 2211-1247 |
| Popis: | Regeneration requires related cells to diverge in fate. We show that activated lymphocytes yield sibling cells with unequal elimination of aged mitochondria. Disparate mitochondrial clearance impacts cell fate and reflects larger constellations of opposing metabolic states. Differentiation driven by an anabolic constellation of PI3K/mTOR activation, aerobic glycolysis, inhibited autophagy, mitochondrial stasis, and ROS production is balanced with self-renewal maintained by a catabolic constellation of AMPK activation, mitochondrial elimination, oxidative metabolism, and maintenance of FoxO1 activity. Perturbations up and down the metabolic pathways shift the balance of nutritive constellations and cell fate owing to self-reinforcement and reciprocal inhibition between anabolism and catabolism. Cell fate and metabolic state are linked by transcriptional regulators, such as IRF4 and FoxO1, with dual roles in lineage and metabolic choice. Instructing some cells to utilize nutrients for anabolism and differentiation while other cells catabolically self-digest and self-renew may enable growth and repair in metazoa. |
| Databáze: | OpenAIRE |
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