Metabolite transporter and metabolic energy balance - from whole organism to sub-cellular regulation in fish

生物体努力在不断变化的环境中维持微妙的能量平衡。在高等生物中，如脊椎动物，在进化过程中各种生理功能的协调部分是通过代谢过程的区隔化来实现的。高效的能量输送系统对于代谢物在各种组织、细胞和亚细胞细胞器之间的分布以维持能量平衡至关重要。我们使用鱼类作为模型来描述代谢物运输系统的精确调节机制与燃料利用偏好之间的代谢联系。糖酵解是存在于所有生物体中的一种代谢能量产生途径，它依赖于葡萄糖作为底物。在正常的生理状态下，葡萄糖穿梭于全身，并在大多数组织中完全用于能量生产。假设在氧气受限的情况下，葡萄糖氧化发生短路，形成乳酸以维持能量平衡。然而，目前，乳酸和其他单羧酸盐（MC）被认为是细胞间和细胞内燃料穿梭的重要代谢中间底物。在鱼类中，与哺乳动物相比，葡萄糖代谢和运输的处理方式不同。一些鱼类对葡萄糖不敏感（即类似于糖尿病状态），而其他鱼类可能主要依赖葡萄糖作为替代燃料供应。我们将研究对MC及其相关运输系统的依赖是否使鱼类比其他脊椎动物具有更大的代谢灵活性。我们采用比较的方法来鉴定骨鱼、板鳃鱼和环口鱼中单羧酸转运体的基因，它们各自具有不同的厌氧能力、燃料偏好和缺氧耐受性。我们将研究在o2限制或其他能量需求过程中从分子到生理水平的运输系统的调节机制。所获得的知识将使研究人员和学生深入了解能量代谢的进化和生物多样性，并阐明许多问题，如鱼类的最佳燃料利用和生长，以及生物医学领域的糖尿病和缺氧耐受性。

Organisms strive to maintain a delicate energy balance in a changing environment. In higher organism, such as vertebrates, the coordination of the various physiological functions over the course of evolution has been partially achieved through the compartmentalization of metabolic processes. An efficient energy transport system becomes vital for metabolite distribution among various tissues, cells, and sub-cellular organelles to maintain an energy balance. We use fish as a model to profile the metabolic links between the precise regulatory mechanism of the metabolite transport system and the preference of fuel utilization. Glycolysis is a metabolic energy production pathway that is present in all organisms, which relies on glucose as a substrate. Under normal physiological states, glucose is shuttled throughout the body and completely used for energy production in most tissues. It has been assumed that under O2 limited situations, glucose oxidation is short-circuited and lactate is formed in an attempt to maintain energy balance. However, currently, lactate and other monocarboxylate (MC) are considered to be important metabolic intermediate substrates for inter- and intra-cellular fuel shuttling. In fish, MC and glucose metabolism and transport are handled differently compared to mammals. Some fish species are glucose insensitive (i.e. similar to a diabetic state) while others may rely mainly on MC as alternative fuel supply. We will investigate if the reliance on MC and its associated transport system afford fish a greater metabolic flexibility than observed in other vertebrates. We take a comparative approach to identify the genes of monocarboxylate transporters in bonyfish, elasmobranches and cyclostomata each of which possess different anaerobic capabilities, fuel preference and hypoxia tolerance. We will examine the regulatory mechanism of the transport system from the molecular to the physiological level under O2-limiting or other energy demanding processes. The knowledge obtained will allow researchers and students to gain insight into the evolution and biodiversity of energy metabolism, and shed light on many issues such as optimal fuel utilization and growth in fish, and diabetics and hypoxia tolerance in the biomedical area.