UMass Chan Medical School Faculty Publications

UMMS Affiliation

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

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


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.


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

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This is an open access article under the CC BY-NC-ND license (

DOI of Published Version



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

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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.