Date of Award
Doctor of Philosophy (PhD)
Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, by altering cristae morphology, fusion in TM cells configures electron transport chain (ETC) complex associations favoring oxidative phosphorylation (OXPHOS) and FAO, while fission in TE cells leads to cristae expansion, reducing ETC efficiency and promoting aerobic glycolysis. Thus mitochondrial remodeling is a signaling mechanism that instructs T cell metabolic programming.
Chair and Committee
Erika L. Pearce
Eugene M. Oltz, Herbert W. Virgin, Paul M. Allen, Takeshi Egawa,
Buck, Michael, "Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming" (2017). Arts & Sciences Electronic Theses and Dissertations. 1091.
Allergy and Immunology Commons, Biology Commons, Cell Biology Commons, Immunology and Infectious Disease Commons, Medical Immunology Commons
Permanent URL: https://doi.org/10.7936/K7GF0RZQ