title: Altered calcium homeostasis in cells transformed by mitochondria from individuals with Parkinson's disease.
abstract: Parkinson's disease may be linked to defects in mitochondrial function. Mitochondrially transformed cells (cybrids) were created from Parkinson's disease patients or disease-free controls. Parkinson's disease cybrids had 26% less complex I activity, but maintained comparable basal calcium and energy levels. Parkinson's disease cybrids recovered from a carbachol-induced increase in cytosolic calcium 53% more slowly than controls even with lanthanum and thapsigargin blockade. Inhibition of complex I with the Parkinson's disease-inducing metabolite 1-methyl-4-phenylpyridinium (MPP+) similarly reduced the rate of recovery after carbachol. This MPP(+)-induced reduction in recovery rates was much more pronounced in control cybrids than in Parkinson's disease cybrids. Parkinson's disease cybrids had less carbonyl cyanide m-chlorophenylhydrazone-releasable calcium. Bypassing complex I with succinate partially restored Parkinson's disease cybrid, and MPP+ suppressed control cybrid recovery rates. The subtle alteration in calcium homeostasis of Parkinson's disease cybrids may reflect an increased susceptibility to cell death under circumstances not ordinarily toxic.
authors.affiliation: Department of Neurological Surgery, University of Virginia, Charlottesville 22908, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Sheehan
authors.forename: R H
authors.initials: RH
authors.lastname: Swerdlow
authors.forename: W D
authors.initials: WD
authors.lastname: Parker
authors.forename: S W
authors.initials: SW
authors.lastname: Miller
authors.forename: R E
authors.initials: RE
authors.lastname: Davis
authors.forename: J B
authors.initials: JB
authors.lastname: Tuttle
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000368:Aged; D002118:Calcium / Q000378:metabolism*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000502:physiology; D004734:Energy Metabolism; D005260:Female; D006706:Homeostasis; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology*; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D007476:Ionophores; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D015655:1-Methyl-4-phenylpyridinium; D002118:Calcium