CAREER: The Molecular Mechanisms of Cold-Induced Mitochondrial Biogenesis

University Of Alaska Fairbanks Campus, Fairbanks AK

Investigators

Abstract

Temperature has a profound effect on the physiology of animals. One modification that occurs in response to a decrease in temperature is an increase in mitochondrial density in some tissues. This process is critical for maintaining aerobic metabolic capacity in animals, yet questions remain about how it is regulated, and why it occurs in some tissues, yet not others. This project will address these questions, using the threespine stickleback Gasterosteus aculetaus as a model organism. This investigation will test the hypothesis that reactive oxygen species (ROS) are produced by mitochondria in response to cold temperature and are required to induce the expression of genes controlling mitochondrial biogenesis. Membrane fluidity decreases as temperature declines and may disrupt the activity of the electron transport chain proteins of the mitochondrion, leading to the formation of ROS. These ROS may directly regulate mitochondrial-biogenic gene expression, or alternatively, high levels of ROS may stimulate the activity of nitric oxide synthase which produces nitric oxide and triggers mitochondrial biogenesis. Both of these possibilities will be tested. Sticklebacks will be maintained at 20 degrees C in the laboratory and then shifted to 5 degrees C and held over a period of six weeks. Throughout the acclimation period, animals will be harvested for measuring levels of ROS, mitochondrial proteins, gene expression, and nitric oxide synthase activity. These parameters will be measured in several tissue types, including those that undergo mitochondrial biogenesis (oxidative skeletal muscle), and those that may not (liver). The differences in response to cold temperature among different tissue types may elucidate the mechanisms underlying the tissue specificity of mitochondrial biogenesis. If ROS and/or NO levels increase during the early stages of cold acclimation, then animals will be treated with inhibitors of ROS and/or NO formation. If either of these free radical species are required to induce mitochondrial biogenesis, then inhibiting their production should prevent increases in mitochondrial density in response to cold temperature. The results from this work will lead to a greater understanding of the molecular mechanisms governing mitochondrial biogenesis. This is a vital process, essential to the health of all organisms. This research will involve undergraduate and graduate Alaska Native students through a collaboration with the Alaska Native Science and Engineering Program at the University of Alaska. These students will also help to develop an outreach program at a local rural school which engages students in learning about the variety of strategies that animals use to survive at cold temperature, with an emphasis on physiological, cellular and molecular adaptations. Students will learn the important role of animals, even those found in local environments, for addressing fundamental questions in biology.