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

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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.