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.