ALTERED CALCIUM HOMEOSTASIS IN CELLS TRANSFORMED BY MITOCHONDRIA FROMINDIVIDUALS WITH PARKINSONS-DISEASE

Parkinson's disease may be linked to defects in mitochondrial function . Mitochondrially transformed cells (cybrids) were created from Parkin son's disease patients or disease-free controls. Parkinson's disease c ybrids had 26% less complex I activity, but maintained comparable basa l calcium and energy levels. Parkinson's disease cybrids recovered fro m a carbachol-induced increase in cytosolic calcium 53% more slowly th an 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 af ter carbachol. This MPP(+)-induced reduction in recovery rates was muc h more pronounced in control cybrids than in Parkinson's disease cybri ds. Parkinson's disease cybrids had less carbonyl cyanide m-chlorophen ylhydrazone-releasable calcium. Bypassing complex I with succinate par tially restored Parkinson's disease cybrid, and MPP(+) suppressed cont rol cybrid recovery rates. The subtle alteration in calcium homeostasi s of Parkinson's disease cybrids may reflect an increased susceptibili ty to cell death under circumstances not ordinarily toxic.