Abstract
Warming events are becoming more frequent and extreme in aquatic environments worldwide. Concurrently, many environments are polluted with biologically active compounds such as pharmaceuticals. Understanding how these challenges interact is critical for understanding the climate crisis, as contaminants may modulate how ectotherms respond to heat stress or vice versa. One potential site for these heat × contaminant interactions is the mitochondrion, which is central to metabolism, implicated in thermal tolerance, and evolutionarily conserved. Using high-resolution respirometry, we investigated how acute warming (to 35 °C, 40 °C, or 45 °C from 25 °C) impacted the respiration, coupling, and metabolic capacity of liver mitochondria isolated from Nile tilapia, and how exposure to environmentally relevant levels of the ubiquitous antidepressant venlafaxine modulated those effects. Mitochondria exposed to hotter temperatures had higher respiration rates and decreased respiratory control ratio compared to mitochondria exposed to cooler temperatures. The depressive effects of venlafaxine on respiration rates through complex I and II or complex II only (State 3 and State 4), as well as complex IV-linked respiration, were mild except in mitochondria exposed to high temperatures, suggesting an interactive effect of warming and contaminant exposure. Finally, we found that the maximal enzyme activity of intact mitochondria (represented by mitochondrial respiration) showed a different pattern of response to warming and venlafaxine compared to its underlying components (as reflected by the activity of succinate dehydrogenase [complex II] and cytochrome c oxidase [complex IV]), demonstrating the value of incorporating both interactive and reductive approaches in understanding how mitochondria cope with anthropogenic changes in the environment.