Abstract
Objective:
Mutations of the mitofusin 2 gene (MFN2) may account for at least a third of the cases of Charcot-Marie-Tooth disease type 2 (CMT2). This study investigates mitochondrial cellular bioenergetics in MFN2-related CMT2A.
Methods:
Mitochondrial network morphology and metabolism were studied in cultures of skin fibroblasts obtained from four CMT2A patients harboring novel missense mutations of the MFN2 gene.
Results:
Although the mitochondrial network appeared morphologically unaltered, there was a significant defect of mitochondrial coupling associated with a reduction of the mitochondrial membrane potential.
Interpretation:
Our results suggest that the sharply reduced efficacy of oxidative phosphorylation in MFN2-related CMT2A may contribute to the pathophysiology of the axonal neuropathy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / metabolism
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Adult
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Apoptosis
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Cells, Cultured
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Charcot-Marie-Tooth Disease / complications*
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Charcot-Marie-Tooth Disease / genetics
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Charcot-Marie-Tooth Disease / pathology*
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DNA Mutational Analysis
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Female
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Fibroblasts / metabolism
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Fibroblasts / ultrastructure
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GTP Phosphohydrolases
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Genetic Predisposition to Disease
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Humans
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Male
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Membrane Potential, Mitochondrial / genetics
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Membrane Potential, Mitochondrial / physiology
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Membrane Proteins / genetics
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Metabolic Networks and Pathways / physiology
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Middle Aged
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Mitochondrial Diseases / etiology*
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Mitochondrial Diseases / genetics
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Mitochondrial Diseases / pathology*
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Mitochondrial Proteins / genetics
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Mutation, Missense
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Reactive Oxygen Species
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Skin / pathology
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Statistics, Nonparametric
Substances
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Membrane Proteins
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Mitochondrial Proteins
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Reactive Oxygen Species
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Adenosine Triphosphate
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GTP Phosphohydrolases
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MFN2 protein, human
Associated data
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OMIM/118210
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OMIM/214400
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OMIM/607706