|Document Type:||Journal Article|
|Title:||Effect of contaminants of emerging concern on liver mitochondrial function in Chinook salmon|
|Author:||Andrew Yeh, David J. Marcinek, James P. Meador, Evan P. Gallagher|
We previously reported the bioaccumulation of contaminants of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) and perfluorinated compounds, in wild juvenile Chinook salmon from urban estuaries of Puget Sound, WA (Meador et al., 2016). Although the toxicological impacts of CECs on salmon are poorly understood, several of the detected contaminants disrupt mitochondrial function in other species. Here, we sought to determine whether environmental exposures to CECs are associated with hepatic mitochondrial dysfunction in juvenile Chinook. Fish were exposed in the laboratory to a dietary mixture of 16 analytes representative of the predominant CECs detected in our field study. Liver mitochondrial content was reduced in fish exposed to CECs, which occurred concomitantly with a 24-32% reduction in expression of peroxisome proliferator-activated receptor (PPAR) ¿ coactivator-1a (pgc-1¿), a positive transcriptional regulator of mitochondrial biogenesis. The laboratory exposures also caused a 40-70% elevation of state 4 respiration per unit mitochondria, which drove a 29-38% reduction of efficiency of oxidative phosphorylation relative to controls. The mixture-induced elevation of respiration was associated with increased oxidative injury as evidenced by increased mitochondrial protein carbonyls, elevated expression of glutathione (GSH) peroxidase 4 (gpx4), a mitochondrial-associated GSH peroxidase that protects against lipid peroxidation, and reduction of mitochondrial GSH. Juvenile Chinook sampled in a WWTP effluent-impacted estuary with demonstrated releases of CECs showed similar trends toward reduced liver mitochondrial content and elevated respiratory activity per mitochondria (including state 3 and uncoupled respiration). Interestingly, respiratory control ratios were greater in fish from the contaminated site relative to fish from a minimally-polluted reference site, which may have been due to differences in the timing of exposure to CECs under laboratory and field conditions. Our results indicate that exposure to CECs can affect both mitochondrial quality and content, and support the analysis of mitochondrial function as an indicator of the sublethal effects of CECs in wild fish.
We hypothesized that environmental exposures to CECs result in dysfunction of liver mitochondria in fish. We utilized juvenile Chinook salmon, an ecologically- and economically-critical species in the Pacific Northwest, and focused on hepatic mitochondria, because the liver is the primary site of xenobiotic biotransformation and a target organ of toxicity for many CECs. Our approach was to characterize the potential impacts of exposure to CECs on mitochondrial ETS function and associated mitochondrial oxidative injury in a subchronic dietary study involving a complex mixture of the predominant analytes representative of field exposures. In a parallel field study, we compared mitochondrial content and function in juvenile Chinook collected from an estuarine field site that receives WWTP effluent, with those from a minimally-polluted reference site.
|Full Text URL:||http://www.sciencedirect.com/science/article/pii/S0166445X17301649?via%3Dihub|
|Theme:||Habitats to Support Sustainable Fisheries and Recovered Populations|
Assess the impacts of toxic chemicals and other pollutants across biological scales, and identify pollution reduction strategies that improve habitat quality.