Exposure to mitochondrial genotoxins and dopaminergic neurodegeneration in Caenorhabditis elegans

Claudia P. González-Hunt, Maxwell C.K. Leung, Rakesh K. Bodhicharla, Madeline G. McKeever, Andrew E. Arrant, Kathleen M. Margillo, Ian T. Ryde, Derek D. Cyr, Sara G. Kosmaczewski, Marc Hammarlund, Joel N. Meyer

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Neurodegeneration has been correlated with mitochondrial DNA (mtDNA) damage and exposure to environmental toxins, but causation is unclear. We investigated the ability of several known environmental genotoxins and neurotoxins to cause mtDNA damage, mtDNA depletion, and neurodegeneration in Caenorhabditis elegans. We found that paraquat, cadmium chloride and aflatoxin B1 caused more mitochondrial than nuclear DNA damage, and paraquat and aflatoxin B1 also caused dopaminergic neurodegeneration. 6-hydroxydopamine (6-OHDA) caused similar levels of mitochondrial and nuclear DNA damage. To further test whether the neurodegeneration could be attributed to the observed mtDNA damage, C. elegans were exposed to repeated low-dose ultraviolet C radiation (UVC) that resulted in persistent mtDNA damage; this exposure also resulted in dopaminergic neurodegeneration. Damage to GABAergic neurons and pharyngeal muscle cells was not detected. We also found that fasting at the first larval stage was protective in dopaminergic neurons against 6-OHDA-induced neurodegeneration. Finally, we found that dopaminergic neurons in C. elegans are capable of regeneration after laser surgery. Our findings are consistent with a causal role for mitochondrial DNA damage in neurodegeneration, but also support non mtDNA-mediated mechanisms.

Original languageEnglish (US)
Article numbere114459
JournalPloS one
Volume9
Issue number12
DOIs
StatePublished - Dec 8 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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