Format

Send to

Choose Destination
Cell. 2016 Jun 30;166(1):63-76. doi: 10.1016/j.cell.2016.05.035. Epub 2016 Jun 9.

Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming.

Author information

1
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
3
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Renal Division, University Medical Center Freiburg, 79106 Freiburg, Germany; Department of Neuroanatomy, University of Freiburg, 79104 Freiburg, Germany.
5
University of California Los Angeles Metabolomics Center, Los Angeles, CA 90095, USA.
6
Academic Medical Center, 1105 AZ Amsterdam, the Netherlands.
7
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
8
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
9
Renal Division, University Medical Center Freiburg, 79106 Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, 79104 Freiburg, Germany.
10
Center for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, 79106 Freiburg, Germany; Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
11
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany. Electronic address: pearce@ie-freiburg.mpg.de.

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.

PMID:
27293185
PMCID:
PMC4974356
DOI:
10.1016/j.cell.2016.05.035
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center