Regulation and Metabolic Networking of Leucine Catabolism

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An organism's ability to maintain a balance between anabolism and catabolism is crucial to achieving net accumulation of biomolecules. In addition, this metabolic balance must be integrated with the rest of the organism's metabolism and remain flexible to respond to a wide variety of developmental and environmental signals. For stationary organisms such as plants, accommodation to environmental parameters is particularly critical. Research on the metabolic function of methylcrotonyl-CoA carboxylase (MCCase) indicates that plant leucine catabolism is networked with other metabolic and physiological processes. Hence, the study of plant leucine catabolism may offer novel insights on how organisms network metabolism to achieve several levels of regulation of complex reticulated processes. This project focuses on the regulation of leucine catabolism in Arabidopsis as an example of how complex interconnected metabolic pathways are controlled to achieve net interconversions of biomolecules. It has been shown that plants catabolize leucine via a mitochondrial pathway that requires the enzyme MCCase. In addition, characterizations of MCCase-deficient genetic stocks indicate that leucine catabolism in plants is shared between mitochondria and peroxisomes. The aim of this project is to elucidate the signaling and regulatory mechanisms that allocate leucine to the mitochondrial versus the peroxisomal catabolic pathways, and to determine how these catabolic pathways are networked with other metabolic processes. To do this, three specific hypotheses will be tested: Hypothesis 1: A block in mitochondrial leucine catabolism is compensated by global shifts in patterns of gene expression. Hypothesis 2: MCCase is the point of integration of leucine catabolism and isoprenoid metabolism. Hypothesis 3: Mitochondrial leucine catabolism is regulated by the metabolic status of the organism in part via changes in MCCase gene transcription. Plants take in simple molecules such as carbon dioxide, and water. Using energy from the sun, these are converted to complex compounds such as starch, proteins, fibers, oils and pharmaceuticals. In addition, these complex compounds are constantly broken down to provide energy for growth as well as to provide the new compounds needed by each plant cell to respond to an ever-changing environment. The net accumulation of useful biomolecules by the plant is thus dependent on the balance between two processes. The long-term goal of this research is to exploit the synergy inherent in a combined genetic and biochemical approach that will ultimately reveal how plants maintain such a balance.