Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming

Michael D D. Buck, David O'Sullivan, Ramon I I. Klein Geltink, Jonathan D D. Curtis, Chih Hao Chang, David E E. Sanin, Jing Qiu, Oliver Kretz, Daniel Braas, Gerritje J J.W. van der Windt, Qiongyu Chen, Stanley Ching Cheng Huang, Christina M M. O'Neill, Brian T T. Edelson, Edward J J. Pearce, Hiromi Sesaki, Tobias B B. Huber, Angelika S S. Rambold, Erika L L. Pearce

Research output: Contribution to journalArticlepeer-review

643 Scopus citations


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.

Original languageEnglish
Pages (from-to)63-76
Number of pages14
Issue number1
StatePublished - Jun 30 2016


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