Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming

Cell Rep. 2018 Dec 11;25(11):3059-3073.e10. doi: 10.1016/j.celrep.2018.11.018.


Mitochondria are key players in the regulation of T cell biology by dynamically responding to cell needs, but how these dynamics integrate in T cells is still poorly understood. We show here that the mitochondrial pro-fission protein Drp1 fosters migration and expansion of developing thymocytes both in vitro and in vivo. In addition, we find that Drp1 sustains in vitro clonal expansion and cMyc-dependent metabolic reprogramming upon activation, also regulating effector T cell numbers in vivo. Migration and extravasation defects are also exhibited in Drp1-deficient mature T cells, unveiling its crucial role in controlling both T cell recirculation in secondary lymphoid organs and accumulation at tumor sites. Moreover, the observed Drp1-dependent imbalance toward a memory-like phenotype favors T cell exhaustion in the tumor microenvironment. All of these findings support a crucial role for Drp1 in several processes during T cell development and in anti-tumor immune-surveillance.

Keywords: Drp1; T cells; cMyc; cell migration; cell proliferation; exhaustion; metabolic reprogramming; mitochondrial dynamics; thymocytes; tumor immune-surveillance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Cell Differentiation
  • Cell Movement*
  • Cell Proliferation
  • Cell Survival
  • Dynamins / metabolism*
  • Homeostasis
  • Immunologic Surveillance*
  • Lymphocyte Activation / immunology
  • Lymphoid Tissue / metabolism
  • MAP Kinase Signaling System
  • Mice, Knockout
  • Phenotype
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Receptors, Antigen, T-Cell
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • Thymocytes / cytology
  • Thymocytes / metabolism


  • Proto-Oncogene Proteins c-myc
  • Receptors, Antigen, T-Cell
  • Dnm1l protein, mouse
  • Dynamins