RRC ID 51512
Author Cho I, Song HO, Cho JH.
Title Mitochondrial Uncoupling Attenuates Age-Dependent Neurodegeneration in C. elegans.
Journal Mol Cells
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.
Volume 40(11)
Pages 864-870
Published 2017-11-30
DOI 10.14348/molcells.2017.0172
PII molcells.2017.0172
PMID 29081084
PMC PMC5712516
MeSH 2,4-Dinitrophenol / pharmacology* 2,4-Dinitrophenol / therapeutic use Aging / genetics* Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Disease Models, Animal Membrane Potential, Mitochondrial / drug effects Mitochondria / drug effects Mitochondria / physiology Mitochondrial Uncoupling Proteins / genetics* Mitochondrial Uncoupling Proteins / metabolism Mitophagy / drug effects Mutation Neurodegenerative Diseases / drug therapy Neurodegenerative Diseases / etiology* Neurodegenerative Diseases / genetics Organophosphonates / pharmacology* Organophosphonates / therapeutic use Piperazines / pharmacology* Piperazines / therapeutic use
IF 4.081
Times Cited 4
C.elegans tm1779