Alternate Modes of Energy Production and clk-1 Life Extension

能量产生的替代模式和 clk-1 寿命延长

• 批准号: 7626207
• 负责人: SHANE L. REA
• 金额: $ 7.99万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7626207
• 关键词: Acetates; Adult; Affect; Aging; Animals; Anions; Attention; Caenorhabditis elegans; Cells; Cessation of life; Condition; Data; Disruption; Electron Transport; Electrons; Environment; Enzymes; Ethanol; Eukaryota; Eukaryotic Cell; Excision; Exhibits; Fermentation; Fumarates; Generations; Hand; Human; Hypoxia; Lead; Life; Life Extension; Longevity; Malates; Measures; Membrane Potentials; Methods; Mitochondria; Nematoda; Organism; Output; Oxidative Phosphorylation; Oxygen; Pathway interactions; Production; Rate; Reactive Oxygen Species; Recording of previous events; Relative (related person); Series; Soil; Standards of Weights and Measures; Succinate Dehydrogenase; Succinates; Superoxides; System; Techniques; Testing; Thermodynamics; Thinking; Time; Work; base; interest; malate; mutant; succinate

DESCRIPTION (provided by applicant): Mitochondrial oxidative phosphorylation provides the major means of energy production in most eucaryotes. complete removal of this capacity often results in premature death. Recent studies using the nematode Caenorhabditis elegans are surprising because they have revealed that disruption of many of the key components of the normal mitochondria! energy-generating machinery do not result in immediate death, rather they typically result in greater than a 30% increase in adult lifespan. Understanding why these so called Mit (Mitochondrial) mutants are long-lived forms the basis of this proposal. We will test the hypothesis that the Mit mutants are long-lived because their crippled mitochondria are maintained and operated under] conditions that lead to a reduction in their reactive oxygen species (ROS) output. C. elegans is naturally a soil dwelling organism. There are times when it is forced to live under low oxygen conditions. As a consequence it has retained several non-oxygen requiring pathways for the generation of ATP and NAD(P)H. Our current data indicates that use of such alternate pathways is one strategy, that the Mit mutants use to supplement their mitochondria! energy deficit. In this study we will also explore the repertoire of alternate energy production pathways used by Mit mutants. We hypothesize that the products generated by these alternate energy production pathways directly interact with Mit mutant mitochondria to affect their operational parameters, including ROS output. The evolutionary history of C. elegans has permitted this species to retain several pathways for making energy in the presence or low or no oxygen. Humans, on the other hand, have retained only some of these. Nonetheless we believe both species have at their disposal the same basic techniques to potentially lower mitochondria! ROS production. Studying Mit mutants can therefore provide us with an understanding of what new operational settings mitochondria must be set at in order to gain life-span extension. It is conceivable that similar settings may also work for our own cells.

描述（申请人提供）：线粒体氧化磷酸化是大多数真核生物产生能量的主要途径。这种能力的完全丧失常常导致过早死亡。最近的研究使用线虫秀丽隐杆线虫是令人惊讶的，因为他们已经发现，破坏许多正常线粒体的关键组成部分！产生能量的机器不会导致立即死亡，相反，它们通常会导致成人寿命增加30%以上。理解为什么这些所谓的Mit（线粒体）突变体是长寿的形式的基础上，这一建议。我们将检验Mit突变体是长寿的假设，因为它们受损的线粒体在导致其活性氧（ROS）输出减少的条件下维持和操作。C.线虫是一种天然的土壤生物。有时它被迫生活在低氧条件下。因此，它保留了几个非氧需要的途径，用于产生ATP和NAD（P）H。我们目前的数据表明，使用这种替代途径是一种策略，Mit突变体使用它来补充线粒体！能量不足在这项研究中，我们还将探讨Mit突变体使用的替代能源生产途径的剧目。我们假设这些替代能量产生途径产生的产物直接与Mit突变体线粒体相互作用，影响其操作参数，包括ROS输出。对C.秀丽隐杆线虫允许这个物种保留几条在有氧或低氧或无氧的情况下制造能量的途径。另一方面，人类只保留了其中的一部分。尽管如此，我们相信这两个物种都有相同的基本技术来降低线粒体的水平！ROS产生。因此，研究Mit突变体可以让我们了解线粒体必须设置什么样的新操作设置才能延长寿命。可以想象，类似的设置也可能适用于我们自己的细胞。