The molecular etiology of human metabolic diseases such as obesity, diabetes and cardiovascular disease is linked to cellular energy metabolism. This involves a network of metabolic pathways and multiple subcellular compartments, for which efficient function relies upon interorganelle coordination. These ongoing studies were initiated to utilize the yeast Saccharomyces cerevisiae as a model system for uncovering mechanisms of fatty acid transport, assimilation and its regulation at the cellular level. Our studies revealed a novel link between mitochondrial membrane transporters, Odc1p, Odc2p, Ymc1p and Ymc2p, thought to transport oxodicarboxylates, and the coordination of peroxisomal fatty acid oxidation with mitochondrial metabolism. The overall goal of our research is to discern the function(s) of these transporters in vivo. Our data indicate that these transporters possess overlapping function(s) that are necessary for glutamate homeostasis and fatty acid oxidation. An array of biochemical/molecular, NMR, cell biological and genetic techniques will be used to more thoroughly understand the relationship between these transporters, glutamate metabolism and fatty acid oxidation. The specific aims to be pursued are: (1) to investigate the activity of the retrograde (mitochondria to nucleus) signaling pathway in transporter mutants, (2) to examine the interplay between these transporters and enzymes involved in fatty acid assimilation and glutamate homeostasis, and (3) to determine the intracellular role(s) of the transporters encoded by YMC1 and YMC2. It is anticipated that the data generated will increase our understanding of the role of mitochondrial transporters in pathways of energy and amino acid metabolism, and also shed light on interorganelle coordination processes in eukaryotes. Our understanding of human metabolic diseases such as obesity, diabetes and cardiovascular disease depends upon elucidation of the regulatory pathways for energy metabolism. These studies utilize a simple cellular system (yeast) to examine the role(s) of intracellular transporters at the crossroads of energy and amino acid metabolism. It is anticipated that advances made in these studies will increase our understanding of the role of such transporters in the control of energy and amino acid metabolism, and shed light on these processes in higher organisms. [unreadable] [unreadable] [unreadable]