Effect of contaminants of emerging concern on liver mitochondrial function in Chinook salmon

•Elevated respiratory activity per liver mitochondria resulted from dietary exposure to a mixture of CECs.•Elevation of state 4 (proton leak) respiration suggested reduced efficiency of oxidative phosphorylation.•Mitochondrial metabolic changes were also associated with oxidative injury in liver mitochondria after dietary exposure.•Field-collected fish exposed to CECs showed similar but less severe trends in mitochondrial metabolism.•Results indicate that exposure to environmentally-relevant mixtures of CECs affects mitochondrial function in fish. We previously reported the bioaccumulation of contaminants of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) and perfluorinated compounds, in field-collected 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) Y coactivator-1a (pgc-1α), 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). However, respiratory control ratios were greater in fish from the contaminated site relative to fish from a minimally-polluted reference site, which