The mitochondrial 3Na+/Ca2+ exchanger NCLX is a hub for cellular and mitochondrial Ca2+ signaling in astrocytes. or Na+: S4-A1

Powered by the mitochondrial membrane potential Ca2+ permeates into the mitochondria via the mitochondrial Ca2+ uniporter and pumped out by the activity of a 3Na+/Ca2+ exchanger. This mitochondrial Ca2+ shuttling is playing a key role in coupling Ca2+ signal to ATP production or regulation of Ca2+ signals in the ER and plasma membrane micro domains while its breakdown leads to mitochondrial Ca2+ overload, the hallmark of brain and cardiac diseases. Despite the importance of mitochondrial Ca2+ shuttling the molecular identity of the uniporter and exchanger remain elusive. In the first part of my talk I will describe the identification of the mitochondrial Na+Ca2+ exchanger termed NCLX and the tools we use to control and monitor its activity. In the second part of my talk I will focus on the physiological role of NCLX in regulating Ca2+ and Na+ signal thereby mediating executive functions ranging from neurotransmission release to proliferation of glial cells. Finally I will describe a novel communication pathway between NCLX with the plasma membrane store operated Ca2+ channel.