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Altered Calcium Homeostasis in Cells Transformed by Mitochondria from Individuals with Parkinson's Disease
Author(s) -
Sheehan J. P.,
Swerdlow R. H.,
Parker W. D.,
Miller S. W.,
Davis R. E.,
Tuttle J. B.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68031221.x
Subject(s) - parkinson's disease , calcium , calcium metabolism , mitochondrion , endocrinology , homeostasis , medicine , disease , chemistry , thapsigargin , biology , biochemistry
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.