Calcineurin subunit B promotes TNF-alpha-induced apoptosis by binding to mitochondria and causing mitochondrial Ca2+ overload.

Previous studies have shown that excess calcineurin subunit B (CnB) associates with mitochondria. Here, CnB overexpression increased CN activity in cells and enhanced TNF-alpha-induced cell death independent of CN activity. Overexpression of CnB increased intracellular Ca2+ concentration, enhanced caspase-3 activity, reduced Bcl-2 expression, and decreased mitochondrial membrane potential, with no change of caspase-8 or p53. CnB bound to isolated mitochondria in a Ca(2+)-dependent manner, and stimulated cytochrome c release from the mitochondria. Altogether, these results demonstrate that CnB is capable of promoting TNF-alpha-induced apoptosis, possibly through effects on mitochondrial functions.