Mitochondrial Ca 2+ Dynamics in MCU Knockout C. elegans Worms.

Mitochondrial [Ca ²⁺ ] plays an important role in the regulation of mitochondrial function, controlling ATP production and apoptosis triggered by mitochondrial Ca ²⁺ overload. This regulation depends on Ca ²⁺ entry into the mitochondria during cell activation processes, which is thought to occur through the mitochondrial Ca ²⁺ uniporter (MCU). Here, we have studied the mitochondrial Ca ²⁺ dynamics in control and MCU-defective C. elegans worms in vivo, by using worms expressing mitochondrially-targeted YC3.60 yellow cameleon in pharynx muscle. Our data show that the small mitochondrial Ca ²⁺ oscillations that occur during normal physiological activity of the pharynx were very similar in both control and MCU-defective worms, except for some kinetic differences that could mostly be explained by changes in neuronal stimulation of the pharynx. However, direct pharynx muscle stimulation with carbachol triggered a large and prolonged increase in mitochondrial [Ca ²⁺ ] that was much larger in control worms than in MCU-defective worms. This suggests that MCU is necessary for the fast mitochondrial Ca ²⁺ uptake induced by large cell stimulations. However, low-amplitude mitochondrial Ca ²⁺ oscillations occurring under more physiological conditions are independent of the MCU and use a different Ca ²⁺ pathway.