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Multiple molecular mechanisms rescue mtDNA disease in C. elegans

(2018) CELL REPORTS. 22(12). p.3115-3125
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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
UNFOLDED-PROTEIN RESPONSE, MITOCHONDRIAL-DNA MUTATIONS, CAENORHABDITIS-ELEGANS, LIFE-SPAN, DYSFUNCTION, MITOPHAGY, STRESS, MICE, ORGANIZATION, SARCOPENIA

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Chicago
Haroon, Suraiya, Annie Li, Jaye L Weinert, Clark Fritsch, Nolan G Ericson, Jasmine Alexander-Floyd, Bart Braeckman, et al. 2018. “Multiple Molecular Mechanisms Rescue mtDNA Disease in  C. Elegans.” Cell Reports 22 (12): 3115–3125.
APA
Haroon, S., Li, A., Weinert, J. L., Fritsch, C., Ericson, N. G., Alexander-Floyd, J., Braeckman, B., et al. (2018). Multiple molecular mechanisms rescue mtDNA disease in  C. elegans. CELL REPORTS, 22(12), 3115–3125.
Vancouver
1.
Haroon S, Li A, Weinert JL, Fritsch C, Ericson NG, Alexander-Floyd J, et al. Multiple molecular mechanisms rescue mtDNA disease in  C. elegans. CELL REPORTS. 2018;22(12):3115–25.
MLA
Haroon, Suraiya et al. “Multiple Molecular Mechanisms Rescue mtDNA Disease in  C. Elegans.” CELL REPORTS 22.12 (2018): 3115–3125. Print.
@article{8558713,
  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.},
  author       = {Haroon, Suraiya and Li, Annie and Weinert, Jaye L and Fritsch, Clark and Ericson, Nolan G and Alexander-Floyd, Jasmine and Braeckman, Bart and Haynes, Cole M and Bielas, Jason H and Gidalevitz, Tali and Vermulst, Marc},
  issn         = {2211-1247},
  journal      = {CELL REPORTS},
  keywords     = {UNFOLDED-PROTEIN RESPONSE,MITOCHONDRIAL-DNA MUTATIONS,CAENORHABDITIS-ELEGANS,LIFE-SPAN,DYSFUNCTION,MITOPHAGY,STRESS,MICE,ORGANIZATION,SARCOPENIA},
  language     = {eng},
  number       = {12},
  pages        = {3115--3125},
  title        = {Multiple molecular mechanisms rescue mtDNA disease in  C. elegans},
  url          = {http://dx.doi.org/10.1016/j.celrep.2018.02.099},
  volume       = {22},
  year         = {2018},
}

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