TY - JOUR
T1 - Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming
AU - Buck, Michael D D.
AU - O'Sullivan, David
AU - Klein Geltink, Ramon I I.
AU - Curtis, Jonathan D D.
AU - Chang, Chih Hao
AU - Sanin, David E E.
AU - Qiu, Jing
AU - Kretz, Oliver
AU - Braas, Daniel
AU - van der Windt, Gerritje J J.W.
AU - Chen, Qiongyu
AU - Huang, Stanley Ching Cheng
AU - O'Neill, Christina M M.
AU - Edelson, Brian T T.
AU - Pearce, Edward J J.
AU - Sesaki, Hiromi
AU - Huber, Tobias B B.
AU - Rambold, Angelika S S.
AU - Pearce, Erika L L.
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/6/30
Y1 - 2016/6/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84976478216&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84976478216&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2016.05.035
DO - 10.1016/j.cell.2016.05.035
M3 - Article
C2 - 27293185
AN - SCOPUS:84976478216
SN - 0092-8674
VL - 166
SP - 63
EP - 76
JO - Cell
JF - Cell
IS - 1
ER -