Normal Mitochondrial DNA and Respiratory Chain Activity in Familial Dysautonomia Fibroblasts

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• 作者：Strasberg ; Paula ; Bridge ; Phillipa ; Merante ; Frank ; Yeger ; Herman ; Pereira ; Jude
• 刊名：Biochemical and Molecular Medicine
• 出版年：1996
• 出版时间：October, 1996
• 年：1996
• 卷：59
• 期：1
• 页码：20-27
• 全文大小：1.32 M

文摘

Familial dysautonomia (FD), an autosomal recessive disease mapped to chromosome 9q31, is a sensory and autonomic neuropathy of unknown etiology. We have previously reported light microscopic pleiomorphic changes in cells suggestive of altered plasma membranes, an increase in globotriaosylceramide (Gb₃), reflected by an increase in Gb₃on the surface of the plasma membrane, and a decrease in the rate and amount of ganglioside synthesized. In unrelated studies, we demonstrated that storage of glycospingolipids (GSL) is deleterious to mitochondrial function. Recently, mitochondrial dysfunction has been associated with neurodegenerative disease, superimposed on an autosomal inheritance pattern. We have now probed Southern blots of total FD fibroblast DNA, digested withBamHI,EcoRII, and/orPvuII, with purified placental³²P-labeled mitochondrial DNA. The sizes of all FD mitochondrial DNAs were normal (16,569 bp), some containing previously identifiedBamHI polymorphisms. Lactate/pyruvate ratios, and activities of Complexes II and III, matched those of control cells. Electron microscopy revealed morphologically normal mitochondria, in conjunction with a normal oxidative state, determined using the redox dyes Mito Tracker CMXR and CMXR-H₂and fluorescence microscopy. We conclude that mitochondrial dysfunction, due to GSL accumulation, changes in mitochondrial DNA, or mutation of a chromosome 9q gene involved in mitochondrial function, is neither a primary nor a secondary cause of FD, as determined by a study of FD fibroblasts.