Abnormal calcium homeostasis and mitochondrial polarization in a human encephalomyopathy

Anna M. Moudy, Shawn D. Handran, Mark P. Goldberg, Natasha Ruffin, Irene Karl, Pamela Kranz-Eble, Darryl C. Devivo, Steven M. Rothman

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95 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)729-733
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number3
DOIs
Publication statusPublished - Jan 31 1995

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ASJC Scopus subject areas

  • Genetics
  • General

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