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KMID : 0578320170400110864
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Molecules and Cells
2017 Volume.40 No. 11 p.864 ~ p.870
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Mitochondrial Uncoupling Attenuates Age-Dependent Neurodegeneration in C. elegans
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Cho In-Jeong
Song Hyun-Ok
Cho Jeong-Hoon
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Abstract
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The uncoupling protein 4 (ucp-4) gene is involved in age-dependent neurodegeneration in C. elegans. Therefore, we aimed to investigate the mechanism underlying the association between mitochondrial uncoupling and neurodegeneration by examining the effects of uncoupling agents and ucp-4 overexpression in C. elegans. Treatment with either DNP or CCCP improved neuronal defects in wild type during aging. Uncoupling agents also restored neuronal phenotypes of ucp-4 mutants to those exhibited by wild type, while ucp-4 overexpression attenuated the severity of age-dependent neurodegeneration. Neuronal improvements were further associated with reductions in mitochondrial membrane potentials. However, these age-dependent neuroprotective effects were limited in mitophagy-deficient mutant, pink-1, background. These results suggest that membrane uncoupling can attenuate age-dependent neurodegeneration by stimulating mitophagy.
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KEYWORD
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aging, C. elegans, mitophagy, neurodegeneration, uncoupling
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