Function, regulation and physiological role of the mitochondrial Na⁺/Ca²⁺ exchanger, NCLX

Mitochondrial Ca²⁺ signaling is linking global cellular Ca²⁺ signals to energy production and controls local Ca²⁺ concentrations in the ER and cell membrane. On the other hand, aberrant change in mitochondrial Ca²⁺ is a hallmark of ischemic and neurodegenerative syndromes. Mitochondrial Ca²⁺ transients are mediated by a Ca²⁺ channel, MCU (mitochondrial Ca²⁺ uniporter), and by a much slower, rate-limiting, mitochondrial Na⁺/Ca²⁺ exchanger, NCLX. This review describes recent studies on the essential role of NCLX in cardiac survival and in diverse physiological activities. It further focuses on the regulatory and transport sites that are controlling NCLX function.