Logo image
Back
Multiple Molecular Mechanisms Rescue mtDNA Disease in C. elegans
Journal article   Open access   Peer reviewed

Multiple Molecular Mechanisms Rescue mtDNA Disease in C. elegans

Suraiya Haroon, Annie Li, Jaye L. Weinert, Clark Fritsch, Nolan G. Ericson, Jasmine Alexander-Floyd, Bart P. Braeckman, Cole M. Haynes, Jason H. Bielas, Tali Gidalevitz, …
Cell reports (Cambridge), v 22(12), pp 3115-3125
20 Mar 2018
DOI: https://doi.org/10.1016/j.celrep.2018.02.099
PMID: 29562168
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/j.celrep.2018.02.099View
Published, Version of Record (VoR)CC BY-NC-ND V4.0,  Open

Abstract

IGF-1/insulin signaling mitochondrial disease mitochondrial DNA depletion mitochondrial genome mitochondrial unfolded protein response mitophagy mutation neuromuscular dysfunction polymerase gamma RNAi
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. [Display omitted] •A genetically engineered worm recapitulates the hallmarks of mtDNA disease in humans•This worm can be exploited to generate countless additional models of mtDNA disease•An RNAi screen identifies 25 genes that can prevent or delay mtDNA disease in worms•IGF-1/insulin signaling, mitophagy, and UPRmt strongly affect disease progression Haroon et al. describe a genetically engineered C. elegans that carries an error-prone copy of DNA polymerase γ, the enzyme that replicates the mitochondrial genome. This worm recapitulates the major hallmarks of mitochondrial disease in humans. The authors identify multiple biological pathways that could potentially delay disease progression.

Metrics

13 Record Views
37 citations in Web of Science
35 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Cell Biology
Logo image