Mitochondria sense with different kinetics the calcium entering into HeLa cells through calcium channels CALHM1 and mutated P86L-CALHM1.
The novel Ca(2+) channel CALHM1 (Calcium Homeostasis Modulator 1) generates cytosolic Ca(2+) transients ([Ca(2+)](c)) that regulate the production of amyloid beta (Abeta). 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 Ca(2+) entering into Hela cells and the Ca(2+) released from the endoplasmic reticulum (ER), in control and in cells transfected with CALHM1 and P86L-CALHM1. We have shown that mitochondria sense Ca(2+) entry in the three cell types; however, the [Ca(2+)](c) and mitochondrial Ca(2+) transients [Ca(2+)](m) had substantially slower kinetics in cells expressing P86L-CALHM1. Mitochondria also sensed the ER Ca(2+) 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 Ca(2+) overload, suggesting how these cells may become more vulnerable to apoptotic stimuli.
Moreno-Ortega
Ana J
AJ
Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, Madrid, Spain.
Ruiz-Nuño
Ana
A
García
Antonio G
AG
Cano-Abad
María F
MF
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D007930:Leucine / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D011392:Proline / Q000235:genetics / Q000378:metabolism
C530077:CALHM1 protein, human; D015220:Calcium Channels; D008562:Membrane Glycoproteins; D011392:Proline; D007930:Leucine; D002118:Calcium