Effects of reduced mitochondrial DNA content on secondary mitochondrial toxicant exposure in Caenorhabditis elegans.

Journal Article (Journal Article)

The mitochondrial genome (mtDNA) is intimately linked to cellular and organismal health, as demonstrated by the fact that mutations in and depletion of mtDNA result in severe mitochondrial disease in humans. However, cells contain hundreds to thousands of copies of mtDNA, which provides genetic redundancy, and creates a threshold effect in which a large percentage of mtDNA must be lost prior to clinical pathogenesis. As certain pharmaceuticals and genetic mutations can result in depletion of mtDNA, and as many environmental toxicants target mitochondria, it is important to understand whether reduced mtDNA will sensitize an individual to toxicant exposure. Here, using ethidium bromide (EtBr), which preferentially inhibits mtDNA replication, we reduced mtDNA 35-55% in the in vivo model organism Caenorhabditis elegans. Chronic, lifelong, low-dose EtBr exposure did not disrupt nematode development or lifespan, and induced only mild alterations in mitochondrial respiration, while having no effect on steady-state ATP levels. Next, we exposed nematodes with reduced mtDNA to the known and suspected mitochondrial toxicants aflatoxin B1, arsenite, paraquat, rotenone or ultraviolet C radiation (UVC). EtBr pre-exposure resulted in mild sensitization of nematodes to UVC and arsenite, had no effect on AfB1 and paraquat, and provided some protection from rotenone toxicity. These mixed results provide a first line of evidence suggesting that reduced mtDNA content may sensitize an individual to certain environmental exposures.

Full Text

Duke Authors

Cited Authors

  • Luz, AL; Meyer, JN

Published Date

  • September 2016

Published In

Volume / Issue

  • 30 /

Start / End Page

  • 255 - 264

PubMed ID

  • 27566481

Pubmed Central ID

  • PMC5023498

Electronic International Standard Serial Number (EISSN)

  • 1872-8278

International Standard Serial Number (ISSN)

  • 1567-7249

Digital Object Identifier (DOI)

  • 10.1016/j.mito.2016.08.014


  • eng