title: Effects of methyl and inorganic mercury exposure on genome homeostasis and mitochondrial function in Caenorhabditis elegans.
abstract: Mercury toxicity mechanisms have the potential to induce DNA damage and disrupt cellular processes, like mitochondrial function. Proper mitochondrial function is important for cellular bioenergetics and immune signaling and function. Reported impacts of mercury on the nuclear genome (nDNA) are conflicting and inconclusive, and mitochondrial DNA (mtDNA) impacts are relatively unknown. In this study, we assessed genotoxic (mtDNA and nDNA), metabolic, and innate immune impacts of inorganic and organic mercury exposure in Caenorhabditis elegans. Genotoxic outcomes measured included DNA damage, DNA damage repair (nucleotide excision repair, NER; base excision repair, BER), and genomic copy number following MeHg and HgCl2exposure alone and in combination with known DNA damage-inducing agents ultraviolet C radiation (UVC) and hydrogen peroxide (H2O2), which cause bulky DNA lesions and oxidative DNA damage, respectively. Following exposure to both MeHg and HgCl2, low-level DNA damage (∼0.25 lesions/10kb mtDNA and nDNA) was observed. Unexpectedly, a higher MeHg concentration reduced damage in both genomes compared to controls. However, this observation was likely the result of developmental delay. In co-exposure treatments, both mercury compounds increased initial DNA damage (mtDNA and nDNA) in combination with H2O2exposure, but had no impact in combination with UVC exposure. Mercury exposure both increased and decreased DNA damage removal via BER. DNA repair after H2O2exposure in mercury-exposed nematodes resulted in damage levels lower than measured in controls. Impacts to NER were not detected. mtDNA copy number was significantly decreased in the MeHg-UVC and MeHg-H2O2co-exposure treatments. Mercury exposure had metabolic impacts (steady-state ATP levels) that differed between the compounds; HgCl2exposure decreased these levels, while MeHg slightly increased levels or had no impact. Both mercury species reduced mRNA levels for immune signaling-related genes, but had mild or no effects on survival on pathogenic bacteria. Overall, mercury exposure disrupted mitochondrial endpoints in a mercury-compound dependent fashion.
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, NC, United States. Electronic address: lauren.h.wyatt@duke.edu.
authors.forename: Lauren H
authors.initials: LH
authors.lastname: Wyatt
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, NC, United States.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Luz
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, United States.
authors.forename: Xiou
authors.initials: X
authors.lastname: Cao
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, NC, United States.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Maurer
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, NC, United States.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Blawas
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, United States.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Aballay
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, NC, United States; Duke Global Health Institute, Duke University, Durham, NC, United States.
authors.forename: William K Y
authors.initials: WK
authors.lastname: Pan
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, NC, United States. Electronic address: joel.meyer@duke.edu.
authors.forename: Joel N
authors.initials: JN
authors.lastname: Meyer
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D018509:DNA, Helminth / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006706:Homeostasis; D006861:Hydrogen Peroxide / Q000633:toxicity; D007700:Kinetics; D008628:Mercury / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D018509:DNA, Helminth; D008767:Methylmercury Compounds; D006861:Hydrogen Peroxide; D008628:Mercury
keywords: Caenorhabditis elegans; Copy number; DNA damage; Innate immunity; Mercury; Mitochondria