FIGURE 1.

Functional and molecular identification of the mitochondrial NCX. a, the first evidence for Na⁺- or Li⁺-dependent mitochondrial Ca²⁺ exchange. Original data were taken from Ref. 12. Li⁺ (▴), Na⁺ (○), or K⁺ (●) was added to isolated mitochondria while monitoring Ca²⁺ efflux. b and c, note that Na⁺ promoted the mitochondrial efflux of Ca²⁺, demonstrating a Na⁺/Ca²⁺ exchange pathway in this organelle. Unlike the plasma membrane NCX family members, the mitochondrial exchanger also mediated Li⁺/Ca²⁺ exchange, indicating that it has distinct functional properties. NCLX was identified as the mitochondrial exchanger. Studies were conducted on cells expressing the mitochondrial Ca²⁺ sensor mito-pericam. Knocking down the expression of mitochondrial NCLX using NCLX siRNA (si NCLX) abolished either Na⁺-dependent (b) or Li⁺-dependent (c) mitochondrial Ca²⁺ efflux. Thus, NCLX shares similar functional properties with the mitochondrial NCX. Original data were taken from Ref. 5. si control, control siRNA.