Metabolic Regulation of Reactive Oxygen Species

Dana-Farber Cancer Inst, Boston MA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): The generation of reactive oxygen species (ROS) is an inevitable consequence of cellular respiration that can wreak havoc on DMA, lipids, and proteins if not detoxified. Ultimately, oxidative stress results in many deleterious effects and is implicated in cancer, neurodegenerative disease, heart disease, stroke, and 'aging. Cells utilize respiration uncoupling proteins to help prevent excessive ROS generation, as well as scavenging enzymes which combat the overaccumulation of ROS. Recently it was found that the transcriptional coactivator PGC-1 alpha is induced in response to ROS and subsequently activates a number of the uncoupling and detoxifying genes. We will determine the transcription factors and activation complex members that PGC-1 alpha interacts with in response to ROS to activate these genes, and resolve the specific functional domains of PGC-1 alpha that are needed for coactivation of two important ROS scavenging enzymes. Our findings will clarify the role of PGC-1 alpha during the transcription of several important ROS detoxifying enzymes, and help to reveal any link to ROS-related diseases. [unreadable] [unreadable] [unreadable]