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.