Ca2+-induced permeability transition in human lymphoblastoid cell mitochondria from normal and Huntington's disease individuals.

摘要: Huntington’s disease (HD) is associated with expansion of polyglutamine tract in a protein named huntingtin (htt) that expressed virtually all body tissues. Thus mutated htt (HD-htt) might affect organs, although clinical manifestations HD are selective loss corticostriatal neurons the brain. In this work we studied how HD-htt affects mitochondria human peripheral blood cells. We compared various functions isolated from cultured lymphoblastoid cells derived three patients juvenile onset (HD-LBM) and age-matched control (C-LBM) individuals. Respiratory parameters different metabolic states, succinate glutamate plus malate were same for cell lines. State 4 membrane potential HD-LBM was slightly lower than C-LBM. The calcium retention capacity (CRC) estimated using simultaneously several methods to register permeability transition (PT). found LBM do not undergo swelling upon Ca2+-induced PT, increase CRC presence ADP + oligomycin. Although each line had values, qualitatively PT C-LBM HD-LBM. With cyclosporin A (CsA) increased significantly, while CsA ineffective. depolarization large pore opening (PT) always occurred simultaneously. at 20–50% Ca2+ loads PT. suggest promotes low H+ conductance by interacting proteins contacts sites without directly promoting or hampering mitochondrial oxidative phosphorylation. (Mol Cell Biochem 269: 143–152, 2005)