Grant: Discovery Grants Program - Individual

To effectively measure the interactive effects of multiple stressors on biological systems, a sensitive indicator of effects that integrates the responses induced by diverse stressors needs to be identified and characterized. My previous research suggests that oxidative stress acting on the mitochondria may be useful in integrating effects of multiple stressors. I therefore propose to probe the idea that diverse environmental stressors induce reactive oxygen species (ROS) leading to oxidative stress that impairs mitochondrial and cellular functions resulting in reduction in performance and fitness or death of the organism. I will test this idea using fish and three common and consequential stressors of aquatic systems: metals, temperature and hypoxia. To avoid shortcomings of previous research that have resulted in inconclusive findings because of investigating a limited number of endpoints, I will employ a holistic approach and interrogate ROS homeostasis from multiple angles. First, I will characterize mitochondrial and cellular ROS metabolism and redox regulation, and unveil how they are modulated by stressors. Second, I will examine how environmental stressors and their interactive effects influence mitochondrial homeostasis, and the role of ROS. Third, I will explore how environmental stressors modulate the relationship among different mitochondrial functional properties. Fourth, I will probe the molecular responses and oxidative modifications induced by ROS including how they are modulated by environmental stressors, and the functional consequences thereof. Overall, the proposed research will contribute fundamentally to our understanding of mitochondrial physiology and the oxidative stress response. Importantly, this research will advance our knowledge of how environmental stressors modulate the diverse effects of ROS that are believed to be the basis of many physiological and pathological states in animals. In practical terms, increased understanding of how combinations of stressors affect fitness of aquatic organisms will lead to better prediction and more effective management of their environmental impacts.