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Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming

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

In: CELL, Vol. 166, No. 1, 30.06.2016, p. 63-76.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Buck, MD, O'Sullivan, D, Klein Geltink, RI, Curtis, JD, Chang, C-H, Sanin, DE, Qiu, J, Kretz, O, Braas, D, van der Windt, GJW, Chen, Q, Huang, SC-C, O'Neill, CM, Edelson, BT, Pearce, EJ, Sesaki, H, Huber, TB, Rambold, AS & Pearce, EL 2016, 'Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming', CELL, vol. 166, no. 1, pp. 63-76. https://doi.org/10.1016/j.cell.2016.05.035

APA

Buck, M. D., O'Sullivan, D., Klein Geltink, R. I., Curtis, J. D., Chang, C-H., Sanin, D. E., Qiu, J., Kretz, O., Braas, D., van der Windt, G. J. W., Chen, Q., Huang, S. C-C., O'Neill, C. M., Edelson, B. T., Pearce, E. J., Sesaki, H., Huber, T. B., Rambold, A. S., & Pearce, E. L. (2016). Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming. CELL, 166(1), 63-76. https://doi.org/10.1016/j.cell.2016.05.035

Vancouver

Buck MD, O'Sullivan D, Klein Geltink RI, Curtis JD, Chang C-H, Sanin DE et al. Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming. CELL. 2016 Jun 30;166(1):63-76. https://doi.org/10.1016/j.cell.2016.05.035

Bibtex

@article{8f4598e324684bd695132d98057ee8e8,
title = "Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming",
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.",
keywords = "Animals, Cell Differentiation, Electron Transport, Fatty Acids, GTP Phosphohydrolases, Glycolysis, Humans, Immunologic Memory, Mice, Mice, Inbred C57BL, Mitochondrial Dynamics, Oxidation-Reduction, Signal Transduction, T-Lymphocytes, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Buck, {Michael D} and David O'Sullivan and {Klein Geltink}, {Ramon I} and Curtis, {Jonathan D} and Chih-Hao Chang and Sanin, {David E} and Jing Qiu and Oliver Kretz and Daniel Braas and {van der Windt}, {Gerritje J W} and Qiongyu Chen and Huang, {Stanley Ching-Cheng} and O'Neill, {Christina M} and Edelson, {Brian T} and Pearce, {Edward J} and Hiromi Sesaki and Huber, {Tobias B} and Rambold, {Angelika S} and Pearce, {Erika L}",
note = "Copyright {\textcopyright} 2016 Elsevier Inc. All rights reserved.",
year = "2016",
month = jun,
day = "30",
doi = "10.1016/j.cell.2016.05.035",
language = "English",
volume = "166",
pages = "63--76",
journal = "CELL",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming

AU - Buck, Michael D

AU - O'Sullivan, David

AU - Klein Geltink, Ramon I

AU - Curtis, Jonathan D

AU - Chang, Chih-Hao

AU - Sanin, David E

AU - Qiu, Jing

AU - Kretz, Oliver

AU - Braas, Daniel

AU - van der Windt, Gerritje J W

AU - Chen, Qiongyu

AU - Huang, Stanley Ching-Cheng

AU - O'Neill, Christina M

AU - Edelson, Brian T

AU - Pearce, Edward J

AU - Sesaki, Hiromi

AU - Huber, Tobias B

AU - Rambold, Angelika S

AU - Pearce, Erika L

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

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.

KW - Animals

KW - Cell Differentiation

KW - Electron Transport

KW - Fatty Acids

KW - GTP Phosphohydrolases

KW - Glycolysis

KW - Humans

KW - Immunologic Memory

KW - Mice

KW - Mice, Inbred C57BL

KW - Mitochondrial Dynamics

KW - Oxidation-Reduction

KW - Signal Transduction

KW - T-Lymphocytes

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.cell.2016.05.035

DO - 10.1016/j.cell.2016.05.035

M3 - SCORING: Journal article

C2 - 27293185

VL - 166

SP - 63

EP - 76

JO - CELL

JF - CELL

SN - 0092-8674

IS - 1

ER -