Mitochondria move in on calcium

Mitochondria aren't just ATP factories. They serve as important components in intracellular signaling by modulating Ca²⁺ and act as a relay system in apoptosis. And they are dynamic organelles, moving about the cell at a rapid pace. On page 661, Yi et al. integrate these observations by demonstrating that local Ca²⁺ concentration controls mitochondrial movement.

Initially, the team was focused on the local interactions between the endoplasmic reticulum (ER) and mitochondria in myoblast cells in culture, but then noticed that changes in Ca²⁺ induced massive fluctuations in the rate of mitochondrial movement. To quantify these changes, the team labeled mitochondria with YFP fused to a mitochondrial targeting sequence. Stimulating the cells with vasopressin, a Ca²⁺ mobilizing hormone, or inducing localized Ca²⁺ release from the ER using IP₃, they found that the mitochondria move most at resting Ca²⁺ concentrations. The organelles came to a standstill when they reached a region with a high concentration of Ca²⁺ (1–2 μM range) and moved again as the Ca²⁺ levels went down.

The mitochondria appear to move along microtubules, yet neither of the known microtubule motors are Ca²⁺-dependent. The team hypothesizes that myosin Va, which binds calmodulin and is probably regulated by Ca²⁺, acts as a bridge between the microtubule motors and the mitochondria. They are currently testing the idea by down-regulating myosin Va.

Mitochondrial arrest in regions of high Ca²⁺ makes biological sense. The organelles would enhance the cell's local Ca²⁺ buffering ability by soaking up the cation. In addition, Ca²⁺ stimulates ATP production in the mitochondria, so the Ca²⁺ influx would induce a local rise in ATP that could be used to drive ATP-dependent Ca²⁺ pumps in the ER and the plasma membrane. Together, the system would help speed the clearance of Ca²⁺, allowing for rapid, short signaling cascades.