Abstract
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.
Committee Chair
Erika L. Pearce
Committee Members
Eugene M. Oltz, Herbert W. Virgin, Paul M. Allen, Takeshi Egawa,
Degree
Doctor of Philosophy (PhD)
Author's Department
Biology & Biomedical Sciences (Immunology)
Document Type
Dissertation
Date of Award
Spring 5-15-2017
Language
English (en)
DOI
https://doi.org/10.7936/K7GF0RZQ
Author's ORCID
https://orcid.org/0000-0002-9611-1199
Recommended Citation
Buck, Michael, "Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming" (2017). Arts & Sciences Theses and Dissertations. 1091.
The definitive version is available at https://doi.org/10.7936/K7GF0RZQ
Comments
Permanent URL: https://doi.org/10.7936/K7GF0RZQ