Am. Moudy et al., ABNORMAL CALCIUM HOMEOSTASIS AND MITOCHONDRIAL POLARIZATION IN A HUMAN ENCEPHALOMYOPATHY, Proceedings of the National Academy of Sciences of the United Statesof America, 92(3), 1995, pp. 729-733
Patients with several inherited human encephalomyopathies exhibit syst
emic and neurological symptoms in association with specific mitochondr
ial mutations. The mechanisms by which these mitochondrial mutations r
esult in cellular injury have not been elucidated. One potential cause
of neuronal vulnerability is an inability to effectively buffer intra
cellular calcium. We report that fibroblasts from patients with one sp
ecific inherited encephalomyopathy, MELAS (mitochondrial encephalomyop
athy, lactic acidosis, and stroke-like episodes) syndrome, have elevat
ed levels of ionized calcium and cannot normally sequester calcium inf
luxes. Quantitative fluorescence imaging demonstrated that this abnorm
ality was associated with a relative decrease in mitochondrial membran
e potential compared to control fibroblasts. This documentation of pat
hological calcium homeostasis in a genetic neurological disease extend
s the calcium hypothesis of toxic cell injury to human mitochondrial e
ncephalomyopathies.