Enhanced NCLX-dependent mitochondrial Ca efflux attenuates pathological remodeling in heart failure.

Mitochondrial calcium (Ca) uptake couples changes in cardiomyocyte energetic demand to mitochondrial ATP production. However, excessive Ca uptake triggers permeability transition and necrosis. Despite these established roles during acute stress, the involvement of Ca signaling in cardiac adaptations to chronic stress remains poorly defined.

The mitochondrial Na/Ca exchanger is essential for Ca homeostasis and viability.

Mitochondrial calcium (Ca) has a central role in both metabolic regulation and cell death signalling, however its role in homeostatic function and disease is controversial. Slc8b1 encodes the mitochondrial Na/Ca exchanger (NCLX), which is proposed to be the primary mechanism for Ca extrusion in excitable cells. Here we show that tamoxifen-induced deletion of Slc8b1 in adult mouse hearts causes sudden death, with less than 13% of affected mice surviving after 14 days.