Coenzyme Q protects Caenorhabditis elegans GAB? neurons from calcium-dependent degeneration.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 107 (2010-08-10), Heft 32, S. 14460-14465
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Zugriff:
Mitochondria are key regulators of cell viability and provide essential functions that protect against neurodegenerative disease. To develop a model for mitochondrial-dependent neurodegeneration in Caenorhabditis elegans, we used RNA interference (RNAi) and genetic ablation to knock down expression of enzymes in the Coenzyme Q (CoQ) biosynthetic pathway. CoQ is a required component of the ATP-producing electron transport chain in mitochondria. We found that reduced levels of CoQ result in a progressive uncoordinated (Unc) phenotype that is correlated with the appearance of degenerating GABA neurons. Both the Unc and degenerative phenotypes emerge during late larval development and progress in adults. Neuron classes in motor and sensory circuits that use other neurotransmitters (dopamine, acetylcholine, glutamate, serotonin) and body muscle cells were less sensitive to CoQ depletion. Our results indicate that the mechanism of GABA neuron degeneration is calcium-dependent and requires activation of the apoptotic gene, ced-4 (Apaf-1). A molecular cascade involving mitochondrial-initiated cell death is also consistent with our finding that GABA neuron degeneration requires the mitochondrial fission gene, drp-1. We conclude that the cell selectivity and developmental progression of CoQ deficiency in C. elegans indicate that this model may be useful for delineating the role of mitochondrial dysfunction in neurodegenerative disease. [ABSTRACT FROM AUTHOR]
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Coenzyme Q protects Caenorhabditis elegans GAB? neurons from calcium-dependent degeneration.
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Autor/in / Beteiligte Person: | Earls, Laurie R. ; Hacker, Mallory L. ; Watson, Joseph D. ; Miller III, David M. |
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Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 107 (2010-08-10), Heft 32, S. 14460-14465 |
Veröffentlichung: | 2010 |
Medientyp: | academicJournal |
ISSN: | 0027-8424 (print) |
DOI: | 10.1073/pnas.0910630107 |
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