The novel Ca2+ channel CALHM1 (Calcium Homeostasis Modulator I generates cytosolic Ca2+ transients ([Ca2+](c)) that regulate the production of amyloid beta (A beta). Its mutated channel P86L-CALHM1 I has been associated to Alzheimer's disease (AD). Using cytosolic- and mitochondrial-targeted aequorins, we have investigated here whether mitochondria sense with similar or different kinetics the Ca2+ entering into Hela cells and the Ca2+ released from the endoplasmic reticulum (ER), in control and in cells transfected with CALIN I and P86L-CALHM1 We have shown that mitochondria sense Ca2+ entry in the three cell types; however. the [Ca2+](c) and mitochondrial Ca2+ transients [Ca2+](m) had substantially slower kinetics in cells expressing P86L-CALHM1 Mitochondria also sensed the ER Ca2+ released by histamine. but ill CALHM1 and P86L-CALHM1 cells the kinetics was faster than that of control cells. Data are compatible with the idea that Mutated CALHM1 may cause mitochondrial Ca2+ overload, suggesting how these cells may become more vulnerable to apoptotic stimuli (C) 2009 Elsevier Inc. All rights reserved