Open AccessAbnormal calcium homeostasis and mitochondrial polarization in a human encephalomyopathy.
Author(s) -
Anna M. Moudy,
Shawn D. Handran,
Mark P. Goldberg,
N.E. Ruffin,
Irene E. Karl,
Pamela Kranz-Eble,
Darryl C. DeVivo,
Steven M. Rothman
Publication year - 1995
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.92.3.729
Subject(s) - mitochondrial encephalomyopathies , mitochondrial encephalomyopathy , lactic acidosis , calcium metabolism , mitochondrial myopathy , biology , calcium , mitochondrion , melas syndrome , medicine , endocrinology , mitochondrial dna , microbiology and biotechnology , genetics , gene
Patients with several inherited human encephalomyopathies exhibit systemic and neurological symptoms in association with specific mitochondrial mutations. The mechanisms by which these mitochondrial mutations result in cellular injury have not been elucidated. One potential cause of neuronal vulnerability is an inability to effectively buffer intracellular calcium. We report that fibroblasts from patients with one specific inherited encephalomyopathy, MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome, have elevated levels of ionized calcium and cannot normally sequester calcium influxes. Quantitative fluorescence imaging demonstrated that this abnormality was associated with a relative decrease in mitochondrial membrane potential compared to control fibroblasts. This documentation of pathological calcium homeostasis in a genetic neurological disease extends the calcium hypothesis of toxic cell injury to human mitochondrial encephalomyopathies.