Mol. Cells 2017; 40(11):   https://doi.org/10.14348/molcells.2017.0172
Mitochondrial Uncoupling Attenuates Age-Dependent Neurodegeneration in C. elegans
Injeong Cho1,3, Hyun-Ok Song2,3, and Jeong Hoon Cho1,*
1Department of Biology Education, College of Education, Chosun University, Gwangju 61452, Korea, 2Department of Infection
Biology, Wonkwang University School of Medicine, Iksan 54538, Korea, 3These authors contributed equally to this work.
Received August 16, 2017; Revised September 8, 2017; Accepted September 21, 2017.; Published online October 27, 2017.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit (http://creativecommons.org/licenses/by-nc-sa/3.0/).
ABSTRACT
The uncoupling protein 4 (ucp-4) gene is involved in agedependent 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.
Keywords: aging, C. elegans, mitophagy, neurodegeneration,
uncoupling


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