The proposed research focuses on a newly identified mammalian molybdenum-dependent enzyme, named mitochondria amidoxime reducing component (mARC2). The mARC enzymes were identified 8 years ago, as part of a prodrug-metabolizing metabolon with cytochrome b5 (CYB5) and cytochrome b5 reductase (CYB5R). Today, the exact physiological function of mARC is still unclear. In an effort to identify a the physiolgical function of mARC2, we recently explored the phenotype of mARC2 knockout mice. My preliminary work establishes that deletion of mARC2 in mice produces (1) significant differences in body composition, (2) decreased fat mass, (3) increased food consumption, (4) increased activity, (5) moderate elevations in energy expenditure, (5) improved fasting glucose and insulin levels, (6) improved glucose clearance, and (7) improved insulin action. Thus, we conclude that mARC-2 deletion improves energy expenditure and glucose homeostasis. Published studies have suggested a role for mARC-2 in regulation of lipogenesis [2-4], however the exact mechanisms at work are not known. Taken together, we hypothesize that mARC-2 is involved in lipogenesis and is a novel target for the treatment of obesity and associated diseases.