The mitochondrial Na⁺/Ca²⁺ exchanger is essential for Ca²⁺ homeostasis and viability.

ABSTRACT: Mitochondrial calcium (_mCa²⁺) 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⁺/Ca²⁺ exchanger (NCLX), which is proposed to be the primary mechanism for _mCa²⁺ 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. Lethality correlated with severe myocardial dysfunction and fulminant heart failure. Mechanistically, cardiac pathology was attributed to _mCa²⁺ overload driving increased generation of superoxide and necrotic cell death, which was

SUBMITTER: Luongo TS 

PROVIDER: S-EPMC5731245 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature