Mitochondria sense with different kinetics the calcium entering into HeLa cells through calcium channels CALHM1 and mutated P86L-CALHM1

Abstract: The novel Ca2+ channel CALHM1 (Calcium Homeostasis Modulator 1) generates cytosolic Ca2+ transients ([Ca2+]c) that regulate the production of amyloid beta (Aβ). Its mutated channel P86L-CALHM1 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 CALHM1 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 in 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. [Copyright &y& Elsevier]