Mitochondrial Uncoupling Attenuates Age-Dependent Neurodegeneration in C. elegans

Molecules and Cells
Injeong ChoJeong Hoon Cho

Abstract

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.

Citations

Feb 2, 2019·Frontiers in Aging Neuroscience·Paloma García-CasasJavier Alvarez
Apr 4, 2021·Cells·Georgios Konstantinidis, Nektarios Tavernarakis

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Methods Mentioned

BETA
transgenic
genetic modifications

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