Metabolic Adaptations of Photoreceptors

光感受器的代谢适应

• 批准号: 8486197
• 负责人: JAMES Bryant HURLEY
• 金额: $ 22.85万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8486197
• 关键词: Amino Acids; Biochemical; Brain; Development; Electromagnetic Energy; Energy Metabolism; Environment; Exploratory/Developmental Grant; Exposure to; Glucose; Glutamine; Goals; Growth; Investigation; Light; Membrane; Metabolic; Metabolism; Mitochondria; Neurons; Outcome; Pathway interactions; Phospholipids; Phosphorylated Peptide; Photoreceptors; Production; Protein Isoforms; Pyruvate Kinase; Radiation; Regulation; Research; Retina; Retinal Diseases; Role; Series; Tyrosine Phosphorylation; aerobic glycolysis; anticancer research; base; cancer cell; design; novel; public health relevance; tumor metabolism

DESCRIPTION (provided by applicant): Photoreceptors are different from neurons in the brain because they are exposed to electromagnetic radiation from the environment. Membranes with the most accumulated exposure to radiation are shed from the tip of the photoreceptor outer segment and replaced by addition of newly synthesized membranes at the base of the outer segment. This type of anabolic activity occurs daily. The high demand for anabolic metabolism during these periods of renewal is reminiscent of the metabolic demands of cancer cells. Recent findings in cancer research have identified important metabolic adaptations of cancer cells that enhance their growth. Specific biochemical mechanisms divert glycolytic intermediates away from energy production and instead into anabolic pathways that support growth. Cancer cells carry out aerobic glycolysis, prefer glutamine as a fuel for their mitochondria and they express a unique form of pyruvate kinase, PKM2 that can be regulated by tyrosine phosphorylation. By reducing PKM2 activity cancer cells divert glycolytic intermediates away from energy production to more anabolic roles like phospholipid synthesis. We have carried out preliminary studies that suggest photoreceptors use some of the same types of adaptations that cancer cells use to enhance their anabolic activity. The goal of this project is to extend discoveries from cancer metabolism research toward an understanding of photoreceptor metabolism. We will explore the novel hypothesis that photoreceptor cells regulate anabolic activity by mechanisms similar to those used by cancer cells. The outcome of this project will be a framework with which to understand how energy metabolism influences photoreceptor function and survival.

描述（由申请人提供）：光感受器与大脑中的神经元不同，因为它们暴露于来自环境的电磁辐射。累积暴露于辐射最多的膜从光感受器外段的尖端脱落，并被外段底部添加的新合成膜所取代。这种类型的合成代谢活动每天都会发生。在这些更新期间对合成代谢的高需求让人想起癌细胞的代谢需求。癌症研究的最新发现已经确定了癌细胞的重要代谢适应，可以促进其生长。特定的生化机制将糖酵解中间体从能量生产中转移到支持生长的合成代谢途径中。癌细胞进行有氧糖酵解，更喜欢谷氨酰胺作为线粒体的燃料，并且它们表达一种独特形式的丙酮酸激酶 PKM2，可以通过酪氨酸磷酸化来调节。通过降低 PKM2 活性，癌细胞将糖酵解中间体从能量产生转移到更多的合成代谢作用，如磷脂合成。我们进行的初步研究表明，光感受器使用一些与癌细胞相同类型的适应来增强其合成代谢活性。该项目的目标是将癌症代谢研究的发现扩展到对光感受器代谢的理解。我们将探索新的假设，即感光细胞通过与癌细胞相似的机制调节合成代谢活动。该项目的成果将是一个框架，用于了解能量代谢如何影响光感受器功能和存活。