Mitochondrial Networking in T Cell Memory

Abstract

T-lymphocytes show large changes in ATP demand and nutrient utilization, imposed by their different roles as T memory and T effector cells. Therefore, T cell remodeling represents a bioenergetic challenge to mitochondria. New work from Buck et al. links changes in mitochondrial shape to T cell fate choice.

The Cerebroventricular Environment Modifies CAR T Cells for Potent Activity against Both Central Nervous System and Systemic Lymphoma

“…significantly lower (P<0.01) NBDG uptake than CD62L-cells ( Figure 7D-E), supporting the memory-like behavior of these CD62L+ cells (33,41). To meet differing energy requirements, effector T cells activate mitochondrial fission and subsequent fragmentation, while memory T cells inhibit mitochondrial fission, leading to mitochondrial elongation (42,43). In line with these reported observations, T cells from ICVtreated mice maintained fused mitochondrial networks that appeared elongated, while T cells from IVtreated mice had punctate mitochondria ( Figure 7F).…”

Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis

“…Naive T cells have a lower proliferation rate and cellular respiration and decreased mitochondrial proteome when compared to activated T cells (Almeida et al, 2016;Buck et al, 2016;Liesa and Shirihai, 2016;Ron-Harel et al, 2016). T cell activation leads to several rounds of cell division, which require the biogenesis of mitochondrial proteins, including those encoded by mtDNA.…”

Mdivi-1, a mitochondrial fission inhibitor, modulates T helper cells and suppresses the development of experimental autoimmune encephalomyelitis

“…The proper functioning of mitochondria in T cells is critical for their activation, differentiation, and function [19]. T cell plasticity is influenced by their metabolism and ATP demand, where mitochondrial morphology plays an important role [14]. Recent research has shown cellular metabolism critically influences T cell differentiation and function, and emerges as a key target for therapy in the treatment of autoimmune diseases, infections, and cancer [19].…”

“…Drp1, a main component of the mitochondrial fission machinery, is a major player in mitochondrial morphology and metabolism. Drp1 inhibition has been observed in T memory cells (T M ) where mitochondria are fused together and have an elongated form; conversely, effector T cells (T E ) have fragmented mitochondria due to an upregulation of Drp1 phosphorylation [14]. Further, Drp1-dependent mitochondrial fission correlates with an increase in ROS production, CD95L-dependent, activation-induced cell death (ACID), and cytokine production in T cells, and inhibition of Drp1 in PHA- or anti-CD3-stimulated T cells results in reduced ROS, ACID, and cytokine production [24].…”