IDOL & MARCH6 E3 ligases in search for physiological meaning

The inducible degrader of the low-density lipoprotein receptor (IDOL) and membrane associated ring CH-type finger 6 (MARCH6) are E3 ubiquitin ligases that regulate the degradation of their target proteins. For IDOL, known targets are members of the low-density lipoprotein receptor, which are involved in the uptake of lipoproteins from the bloodstream into the cell. In the first half of this thesis, experiments into the role of IDOL in the metabolic syndrome and intestinal cells are presented, as well as an overview of current literature on IDOL and commentaries on papers of other authors that explored the role of IDOL.
For MARCH6, known targets include a rate limiting enzyme in cholesterol biosynthesis (squalene epoxidase), a lipid droplet associated protein (perilipin 2) and a thyroid hormone activating enzyme (deiodinase 2), but a role for MARCH6 in more general protein degradation pathways has also been observed. In the second part of this thesis, the potential role of MARCH6 in thermogenesis, atherosclerosis and hepatic lipid metabolism is explored.