University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

UMass Metabolic Network; Department of Molecular, Cell, and Cancer Biology

Publication Date

2018-03-20

Document Type

Article

Disciplines

Cell Biology | Cellular and Molecular Physiology | Genetics and Genomics | Molecular Biology | Nutritional and Metabolic Diseases

Abstract

Genetic instability of the mitochondrial genome (mtDNA) plays an important role in human aging and disease. Thus far, it has proven difficult to develop successful treatment strategies for diseases that are caused by mtDNA instability. To address this issue, we developed a model of mtDNA disease in the nematode C. elegans, an animal model that can rapidly be screened for genes and biological pathways that reduce mitochondrial pathology. These worms recapitulate all the major hallmarks of mtDNA disease in humans, including increased mtDNA instability, loss of respiration, reduced neuromuscular function, and a shortened lifespan. We found that these phenotypes could be rescued by intervening in numerous biological pathways, including IGF-1/insulin signaling, mitophagy, and the mitochondrial unfolded protein response, suggesting that it may be possible to ameliorate mtDNA disease through multiple molecular mechanisms.

Keywords

IGF-1/insulin signaling, RNAi, mitochondrial DNA depletion, mitochondrial disease, mitochondrial genome, mitochondrial unfolded protein response, mitophagy, mutation, neuromuscular dysfunction, polymerase gamma

Rights and Permissions

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI of Published Version

10.1016/j.celrep.2018.02.099

Source

Cell Rep. 2018 Mar 20;22(12):3115-3125. doi: 10.1016/j.celrep.2018.02.099. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Cell reports

PubMed ID

29562168

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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