Mitochondria (white, bottom) move toward the immune synapse (right) to help prevent calcium from closing calcium channels.

HOTH/NAS

Arendezvous among mitochondria and the juncture between immune cells is needed to jumpstart T cells, according to results from Ariel Quintana, Markus Hoth, and colleagues (Saarland University, Homburg, Germany). The mitochondria soak up calcium to keep nearby calcium channels open.

Calcium flowing into a T cell that has met an antigen-presenting cell turns on transcription factors that activate the T cell. The calcium enters through channels in the plasma membrane that then close when calcium levels rise. For the channels to stay open long enough for an effective signal, mitochondria have to soak up some of this influx. The new results show that, to be successful sponges, mitochondria have to be in the right place.

That place is the meeting point, called the immune synapse, between the T cell and its antigen-presenting partner. This ring of receptors and adhesion molecules links the cells while the T cell becomes activated. The authors found that synapse formation was followed by relocation of T cell mitochondria to the synapse membrane.

Mitochondria snuggled up to within 200 nm of the plasma membrane, leading the authors to suspect that a physical linkage might exist. This huddle was needed for maximum calcium influx and T cell activation.

As in other cell types, T cell mitochondria required microtubule tracks for their travels. But actin was also necessary. Cortical actin is reorganized during synapse formation and might pull microtubule tracks into position to aim mitochondria in the right direction. Whether T cells regulate this migration—perhaps blocking it to avoid activation—is not yet clear.

In cells in which a few mitochondria avoided the journey, calcium was mainly taken in by those that made the trip. This mopping up redistributes the calcium elsewhere, away from the calcium-sensitive channels. “I guess that means the channels are also at the synapse,” says Hoth. Concentrating calcium influx at the synapse might point vesicle fusion (a calcium-draining activity) toward the attached cell—a handy way to localize the secretion of cytokines by T helper cells or cytotoxic granules by killer T cells.

Reference:

Quintana, A., et al.
2007
.
Proc. Natl. Acad. Sci. USA.
104
:
14418
–14423.