Mitochondrial Ca Dynamics in MCU Knockout Worms.

Mitochondrial [Ca] plays an important role in the regulation of mitochondrial function, controlling ATP production and apoptosis triggered by mitochondrial Ca overload. This regulation depends on Ca entry into the mitochondria during cell activation processes, which is thought to occur through the mitochondrial Ca uniporter (MCU). Here, we have studied the mitochondrial Ca dynamics in control and MCU-defective worms in vivo, by using worms expressing mitochondrially-targeted YC3.60 yellow cameleon in pharynx muscle. Our data show that the small mitochondrial Ca 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] that was much larger in control worms than in MCU-defective worms. This suggests that MCU is necessary for the fast mitochondrial Ca uptake induced by large cell stimulations. However, low-amplitude mitochondrial Ca oscillations occurring under more physiological conditions are independent of the MCU and use a different Ca pathway.